Shiladitya Sengupta, PhD

Shiladitya Sengupta, PhD, joined Scientific Publications and Grants Department at the Texas Heart Institute as a senior scientific grant writer in December 2018. He received his doctoral degree in Life Sciences from Jadavpur University, India in 2008. Before joining Texas Heart Institute, he worked at Houston Methodist Research Institute and University of Texas Medical Branch at Galveston as a research scientist. His research interest was on genome damage repair and transcriptional regulation. He was a Keck Fellow of CPRIT funded Gulf Coast Consortia’s Computational Cancer Biology Training Program. He spends quality time with family and enjoys cooking and traveling.

Show full bio

Shiladitya Sengupta, PhD, joined Scientific Publications and Grants Department at the Texas Heart Institute as a senior scientific grant writer in December 2018. He received his doctoral degree in Life Sciences from Jadavpur University, India in 2008. Before joining Texas Heart Institute, he worked at Houston Methodist Research Institute and University of Texas Medical Branch at Galveston as a research scientist. His research interest was on genome damage repair and transcriptional regulation. He was a Keck Fellow of CPRIT funded Gulf Coast Consortia’s Computational Cancer Biology Training Program. He spends quality time with family and enjoys cooking and traveling.

See Publications

Texas Heart Institute Positions

Education

  • Undergraduate:

    University of Calcutta, India

  • Postgraduate:

    Jadavpur University (India), University of Texas Medical Branch at Galveston

Honors, Awards and Memberships

  • Young Scientist Award
  • Indian Society of Human Genetics

Publications

4862227 X4LHCUID 1 alternatives-to-animal-experimentation 10 date desc Sengupta 16281 https://www.texasheart.org/wp-content/plugins/zotpress/
%7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3Afalse%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%22ESNZI96Q%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Bacolla%20et%20al.%22%2C%22parsedDate%22%3A%222021-01-11%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BBacolla%2C%20A.%2C%20%26lt%3Bstrong%26gt%3BSengupta%26lt%3B%5C%2Fstrong%26gt%3B%2C%20S.%2C%20Ye%2C%20Z.%20et%20al.%20%282021%29.%20Heritable%20pattern%20of%20oxidized%20DNA%20base%20repair%20coincides%20with%20pre-targeting%20of%20repair%20complexes%20to%20open%20chromatin.%20%26lt%3Bi%26gt%3BNucleic%20Acids%20Res%26lt%3B%5C%2Fi%26gt%3B%20%26lt%3Bi%26gt%3B49%26lt%3B%5C%2Fi%26gt%3B%2C%20221%26%23x2013%3B243.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1093%5C%2Fnar%5C%2Fgkaa1120%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1093%5C%2Fnar%5C%2Fgkaa1120%26lt%3B%5C%2Fa%26gt%3B.%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Heritable%20pattern%20of%20oxidized%20DNA%20base%20repair%20coincides%20with%20pre-targeting%20of%20repair%20complexes%20to%20open%20chromatin%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Albino%22%2C%22lastName%22%3A%22Bacolla%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Shiladitya%22%2C%22lastName%22%3A%22Sengupta%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Zu%22%2C%22lastName%22%3A%22Ye%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Chunying%22%2C%22lastName%22%3A%22Yang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Joy%22%2C%22lastName%22%3A%22Mitra%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ruth%20B.%22%2C%22lastName%22%3A%22De-Paula%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Muralidhar%20L.%22%2C%22lastName%22%3A%22Hegde%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Zamal%22%2C%22lastName%22%3A%22Ahmed%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Matthew%22%2C%22lastName%22%3A%22Mort%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22David%20N.%22%2C%22lastName%22%3A%22Cooper%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Sankar%22%2C%22lastName%22%3A%22Mitra%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22John%20A.%22%2C%22lastName%22%3A%22Tainer%22%7D%5D%2C%22abstractNote%22%3A%22Human%20genome%20stability%20requires%20efficient%20repair%20of%20oxidized%20bases%2C%20which%20is%20initiated%20via%20damage%20recognition%20and%20excision%20by%20NEIL1%20and%20other%20base%20excision%20repair%20%28BER%29%20pathway%20DNA%20glycosylases%20%28DGs%29.%20However%2C%20the%20biological%20mechanisms%20underlying%20detection%20of%20damaged%20bases%20among%20the%20million-fold%20excess%20of%20undamaged%20bases%20remain%20enigmatic.%20Indeed%2C%20mutation%20rates%20vary%20greatly%20within%20individual%20genomes%2C%20and%20lesion%20recognition%20by%20purified%20DGs%20in%20the%20chromatin%20context%20is%20inefficient.%20Employing%20super-resolution%20microscopy%20and%20co-immunoprecipitation%20assays%2C%20we%20find%20that%20acetylated%20NEIL1%20%28AcNEIL1%29%2C%20but%20not%20its%20non-acetylated%20form%2C%20is%20predominantly%20localized%20in%20the%20nucleus%20in%20association%20with%20epigenetic%20marks%20of%20uncondensed%20chromatin.%20Furthermore%2C%20chromatin%20immunoprecipitation%20followed%20by%20high-throughput%20sequencing%20%28ChIP-seq%29%20revealed%20non-random%20AcNEIL1%20binding%20near%20transcription%20start%20sites%20of%20weakly%20transcribed%20genes%20and%20along%20highly%20transcribed%20chromatin%20domains.%20Bioinformatic%20analyses%20revealed%20a%20striking%20correspondence%20between%20AcNEIL1%20occupancy%20along%20the%20genome%20and%20mutation%20rates%2C%20with%20AcNEIL1-occupied%20sites%20exhibiting%20fewer%20mutations%20compared%20to%20AcNEIL1-free%20domains%2C%20both%20in%20cancer%20genomes%20and%20in%20population%20variation.%20Intriguingly%2C%20from%20the%20evolutionarily%20conserved%20unstructured%20domain%20that%20targets%20NEIL1%20to%20open%20chromatin%2C%20its%20damage%20surveillance%20of%20highly%20oxidation-susceptible%20sites%20to%20preserve%20essential%20gene%20function%20and%20to%20limit%20instability%20and%20cancer%20likely%20originated%20%5Cu223c500%20million%20years%20ago%20during%20the%20buildup%20of%20free%20atmospheric%20oxygen.%22%2C%22date%22%3A%22Jan%2011%2C%202021%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1093%5C%2Fnar%5C%2Fgkaa1120%22%2C%22ISSN%22%3A%221362-4962%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22X4LHCUID%22%5D%2C%22dateModified%22%3A%222021-02-11T16%3A51%3A04Z%22%7D%7D%2C%7B%22key%22%3A%22UZUT6EM3%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Sengupta%20et%20al.%22%2C%22parsedDate%22%3A%222020-09-08%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3B%26lt%3Bstrong%26gt%3BSengupta%26lt%3B%5C%2Fstrong%26gt%3B%2C%20S.%2C%20Wang%2C%20H.%2C%20Yang%2C%20C.%20et%20al.%20%282020%29.%20Ligand-induced%20gene%20activation%20is%20associated%20with%20oxidative%20genome%20damage%20whose%20repair%20is%20required%20for%20transcription.%20%26lt%3Bi%26gt%3BProc%20Natl%20Acad%20Sci%20U%20S%20A%26lt%3B%5C%2Fi%26gt%3B%20%26lt%3Bi%26gt%3B117%26lt%3B%5C%2Fi%26gt%3B%2C%2022183%26%23x2013%3B22192.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1073%5C%2Fpnas.1919445117%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1073%5C%2Fpnas.1919445117%26lt%3B%5C%2Fa%26gt%3B.%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Ligand-induced%20gene%20activation%20is%20associated%20with%20oxidative%20genome%20damage%20whose%20repair%20is%20required%20for%20transcription%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Shiladitya%22%2C%22lastName%22%3A%22Sengupta%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Haibo%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Chunying%22%2C%22lastName%22%3A%22Yang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Bartosz%22%2C%22lastName%22%3A%22Szczesny%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Muralidhar%20L.%22%2C%22lastName%22%3A%22Hegde%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Sankar%22%2C%22lastName%22%3A%22Mitra%22%7D%5D%2C%22abstractNote%22%3A%22Among%20several%20reversible%20epigenetic%20changes%20occurring%20during%20transcriptional%20activation%2C%20only%20demethylation%20of%20histones%20and%20cytosine-phosphate-guanines%20%28CpGs%29%20in%20gene%20promoters%20and%20other%20regulatory%20regions%20by%20specific%20demethylase%28s%29%20generates%20reactive%20oxygen%20species%20%28ROS%29%2C%20which%20oxidize%20DNA%20and%20other%20cellular%20components.%20Here%2C%20we%20show%20induction%20of%20oxidized%20bases%20and%20single-strand%20breaks%20%28SSBs%29%2C%20but%20not%20direct%20double-strand%20breaks%20%28DSBs%29%2C%20in%20the%20genome%20during%20gene%20activation%20by%20ligands%20of%20the%20nuclear%20receptor%20superfamily.%20We%20observed%20that%20these%20damages%20were%20preferentially%20repaired%20in%20promoters%20via%20the%20base%20excision%20repair%20%28BER%29%5C%2Fsingle-strand%20break%20repair%20%28SSBR%29%20pathway.%20Interestingly%2C%20BER%5C%2FSSBR%20inhibition%20suppressed%20gene%20activation.%20Constitutive%20association%20of%20demethylases%20with%20BER%5C%2FSSBR%20proteins%20in%20multiprotein%20complexes%20underscores%20the%20coordination%20of%20histone%5C%2FDNA%20demethylation%20and%20genome%20repair%20during%20gene%20activation.%20However%2C%20ligand-independent%20transcriptional%20activation%20occurring%20during%20heat%20shock%20%28HS%29%20induction%20is%20associated%20with%20the%20generation%20of%20DSBs%2C%20the%20repair%20of%20which%20is%20likewise%20essential%20for%20the%20activation%20of%20HS-responsive%20genes.%20These%20observations%20suggest%20that%20the%20repair%20of%20distinct%20damages%20induced%20during%20diverse%20transcriptional%20activation%20is%20a%20universal%20prerequisite%20for%20transcription%20initiation.%20Because%20of%20limited%20investigation%20of%20demethylation-induced%20genome%20damage%20during%20transcription%2C%20this%20study%20suggests%20that%20the%20extent%20of%20oxidative%20genome%20damage%20resulting%20from%20various%20cellular%20processes%20is%20substantially%20underestimated.%22%2C%22date%22%3A%22Sep%2008%2C%202020%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1073%5C%2Fpnas.1919445117%22%2C%22ISSN%22%3A%221091-6490%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22X4LHCUID%22%5D%2C%22dateModified%22%3A%222020-10-13T17%3A43%3A08Z%22%7D%7D%2C%7B%22key%22%3A%223RS3VD2W%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Bhakat%20et%20al.%22%2C%22parsedDate%22%3A%222020-09%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BBhakat%2C%20K.%20K.%2C%20%26lt%3Bstrong%26gt%3BSengupta%26lt%3B%5C%2Fstrong%26gt%3B%2C%20S.%20and%20Mitra%2C%20S.%20%282020%29.%20Fine-tuning%20of%20DNA%20base%20excision%5C%2Fstrand%20break%20repair%20via%20acetylation.%20%26lt%3Bi%26gt%3BDNA%20Repair%20%28Amst%29%26lt%3B%5C%2Fi%26gt%3B%20%26lt%3Bi%26gt%3B93%26lt%3B%5C%2Fi%26gt%3B%2C%20102931.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1016%5C%2Fj.dnarep.2020.102931%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1016%5C%2Fj.dnarep.2020.102931%26lt%3B%5C%2Fa%26gt%3B.%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Fine-tuning%20of%20DNA%20base%20excision%5C%2Fstrand%20break%20repair%20via%20acetylation%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Kishor%20K.%22%2C%22lastName%22%3A%22Bhakat%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Shiladitya%22%2C%22lastName%22%3A%22Sengupta%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Sankar%22%2C%22lastName%22%3A%22Mitra%22%7D%5D%2C%22abstractNote%22%3A%22In%20addition%20to%20the%20key%20roles%20of%20reversible%20acetylation%20of%20histones%20in%20chromatin%20in%20epigenetic%20regulation%20of%20gene%20expression%2C%20acetylation%20of%20nonhistone%20proteins%20by%20histone%20acetyltransferases%20%28HATs%29%20p300%20and%20CBP%20is%20involved%20in%20DNA%20transactions%2C%20including%20repair%20of%20base%20damages%20and%20strand%20breaks.%20We%20characterized%20acetylation%20of%20human%20NEIL1%20DNA%20glycosylase%20and%20AP-endonuclease%201%20%28APE1%29%2C%20which%20initiate%20repair%20of%20oxidized%20bases%20and%20single-strand%20breaks%20%28SSBs%29%2C%20respectively.%20Acetylation%20induces%20localized%20conformation%20change%20because%20of%20neutralization%20of%20the%20positive%20charge%20of%20specific%20acetyl-acceptor%20Lys%20residues%2C%20which%20are%20often%20present%20in%20clusters.%20Acetylation%20in%20NEIL1%2C%20APE1%2C%20and%20possibly%20other%20base%20excision%20repair%20%28BER%29%5C%2FSSB%20repair%20%28SSBR%29%20enzymes%20by%20HATs%2C%20prebound%20to%20chromatin%2C%20induces%20assembly%20of%20active%20repair%20complexes%20on%20the%20chromatin.%20In%20this%20review%2C%20we%20discuss%20the%20roles%20of%20acetylation%20of%20NEIL1%20and%20APE1%20in%20modulating%20their%20activities%20and%20complex%20formation%20with%20other%20proteins%20for%20fine-tuning%20BER%20in%20chromatin.%20Further%2C%20the%20implications%20of%20promoter%5C%2Fenhancer-bound%20acetylated%20BER%20protein%20complexes%20in%20the%20regulation%20of%20transcriptional%20activation%2C%20mediated%20by%20complex%20interplay%20of%20acetylation%20and%20demethylation%20of%20histones%20are%20discussed.%22%2C%22date%22%3A%22Sept%202020%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1016%5C%2Fj.dnarep.2020.102931%22%2C%22ISSN%22%3A%221568-7856%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22X4LHCUID%22%5D%2C%22dateModified%22%3A%222020-11-11T20%3A31%3A22Z%22%7D%7D%2C%7B%22key%22%3A%22A3K2MTGM%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Sengupta%20et%20al.%22%2C%22parsedDate%22%3A%222018-12-11%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3B%26lt%3Bstrong%26gt%3BSengupta%26lt%3B%5C%2Fstrong%26gt%3B%2C%20S.%2C%20Yang%2C%20C.%2C%20Eckelmann%2C%20B.%20J.%20et%20al.%20%282018%29.%20Regulation%20of%20Oxidized%20Base%20Repair%20in%20Human%20Chromatin%20by%20Posttranslational%20Modification.%20In%20%26lt%3Bi%26gt%3BAdvances%20in%20DNA%20Repair%26lt%3B%5C%2Fi%26gt%3B.%20Available%20at%3A%20%26lt%3Ba%20class%3D%26%23039%3Bzp-ItemURL%26%23039%3B%20href%3D%26%23039%3Bhttps%3A%5C%2F%5C%2Fwww.intechopen.com%5C%2Fonline-first%5C%2Fregulation-of-oxidized-base-repair-in-human-chromatin-by-posttranslational-modification%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fwww.intechopen.com%5C%2Fonline-first%5C%2Fregulation-of-oxidized-base-repair-in-human-chromatin-by-posttranslational-modification%26lt%3B%5C%2Fa%26gt%3B%20%5BAccessed%20February%206%2C%202019%5D.%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22bookSection%22%2C%22title%22%3A%22Regulation%20of%20Oxidized%20Base%20Repair%20in%20Human%20Chromatin%20by%20Posttranslational%20Modification%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Shiladitya%22%2C%22lastName%22%3A%22Sengupta%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Chunying%22%2C%22lastName%22%3A%22Yang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Bradley%20J.%22%2C%22lastName%22%3A%22Eckelmann%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Muralidhar%20L.%22%2C%22lastName%22%3A%22Hegde%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Sankar%22%2C%22lastName%22%3A%22Mitra%22%7D%5D%2C%22abstractNote%22%3A%22Base%20excision%20repair%20%28BER%29%20is%20the%20major%20pathway%20for%20the%20repair%20of%20oxidized%20bases%20and%20apurinic%5C%2Fapyrimidinic%20%28abasic%3B%20AP%29%20sites%20produced%20by%20reaction%20with%20reactive%20oxygen%5C%2Fnitrogen%20species%20%28ROS%5C%2FRNS%29.%20These%20metabolites%20are%20generated%20spontaneously%20by%20endogenous%20cellular%20processes%20and%20also%20by%20environmental%20agents.%20Because%20most%20of%20these%20lesions%20are%20promutagenic%2C%20linked%20to%20diverse%20disease-associated%20somatic%20mutations%2C%20as%20well%20as%20heritable%20single%20nucleotide%20polymorphisms%20%28SNPs%29%20in%20the%20normal%20human%20population%2C%20their%20prompt%20repair%20is%20warranted.%20Impairment%20of%20repair%20leading%20to%20mutation%2C%20a%20hallmark%20of%20cancer%2C%20underscores%20the%20essentiality%20of%20BER%20for%20maintaining%20genome%20integrity%20in%20humans%20and%20other%20mammals.%20In%20mammals%2C%20repair%20of%20oxidized%20bases%20and%20other%20BER%20substrates%20is%20initiated%20by%20DNA%20glycosylases%20%28DGs%29%2C%20which%20excise%20the%20damaged%20bases%20and%20cleave%20the%20DNA%20strands%20at%20the%20resulting%20AP%20sites%2C%20followed%20by%20sequential%20end%20processing%2C%20gap-filling%20DNA%20synthesis%2C%20and%20ligation.%20In%20vitro%20BER%20performed%20with%20naked%20DNA%20substrates%20has%20been%20extensively%20studied%2C%20which%20delineates%20its%20basic%20mechanistic%20steps%20and%20subpathways.%20However%2C%20recent%20interest%20is%20directed%20to%20unraveling%20BER%20in%20cell%20chromatin%2C%20including%20its%20regulation%20via%20posttranslational%20modifications%20%28PTMs%29%2C%20which%20occurs%20possibly%20in%20concert%20with%20nucleosome%20remodeling.%20Emerging%20reports%20on%20various%20PTMs%20of%20BER%20enzymes%20indicate%20that%20the%20PTMs%2C%20while%20dispensable%20for%20the%20enzymatic%20activity%2C%20regulate%20overall%20repair%20by%20modulating%20interactions%20with%20other%20repair%20proteins%20and%20chromatin%20factors%2C%20assembly%20of%20BER%20complexes%2C%20as%20well%20as%20turnover%20of%20the%20proteins%2C%20and%20may%20ultimately%20dictate%20the%20cellular%20phenotype.%20Here%2C%20we%20discuss%20recent%20advances%20in%20the%20BER%20field%20by%20reviewing%20the%20PTMs%20and%20how%20they%20regulate%20BER%20in%20chromatin.%22%2C%22bookTitle%22%3A%22Advances%20in%20DNA%20Repair%22%2C%22date%22%3A%222018-12-11%22%2C%22language%22%3A%22en%22%2C%22ISBN%22%3A%22%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.intechopen.com%5C%2Fonline-first%5C%2Fregulation-of-oxidized-base-repair-in-human-chromatin-by-posttranslational-modification%22%2C%22collections%22%3A%5B%22X4LHCUID%22%5D%2C%22dateModified%22%3A%222019-02-06T15%3A18%3A25Z%22%7D%7D%2C%7B%22key%22%3A%22ZUCJIECS%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Sengupta%20et%20al.%22%2C%22parsedDate%22%3A%222018%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3B%26lt%3Bstrong%26gt%3BSengupta%26lt%3B%5C%2Fstrong%26gt%3B%2C%20S.%2C%20Yang%2C%20C.%2C%20Hegde%2C%20M.%20L.%20et%20al.%20%282018%29.%20Acetylation%20of%20oxidized%20base%20repair-initiating%20NEIL1%20DNA%20glycosylase%20required%20for%20chromatin-bound%20repair%20complex%20formation%20in%20the%20human%20genome%20increases%20cellular%20resistance%20to%20oxidative%20stress.%20%26lt%3Bi%26gt%3BDNA%20Repair%26lt%3B%5C%2Fi%26gt%3B%20%26lt%3Bi%26gt%3B66%26%23x2013%3B67%26lt%3B%5C%2Fi%26gt%3B%2C%201%26%23x2013%3B10.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1016%5C%2Fj.dnarep.2018.04.001%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1016%5C%2Fj.dnarep.2018.04.001%26lt%3B%5C%2Fa%26gt%3B.%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Acetylation%20of%20oxidized%20base%20repair-initiating%20NEIL1%20DNA%20glycosylase%20required%20for%20chromatin-bound%20repair%20complex%20formation%20in%20the%20human%20genome%20increases%20cellular%20resistance%20to%20oxidative%20stress%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S.%22%2C%22lastName%22%3A%22Sengupta%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22C.%22%2C%22lastName%22%3A%22Yang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22M.L.%22%2C%22lastName%22%3A%22Hegde%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22P.M.%22%2C%22lastName%22%3A%22Hegde%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.%22%2C%22lastName%22%3A%22Mitra%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%22%2C%22lastName%22%3A%22Pandey%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%22%2C%22lastName%22%3A%22Dutta%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.T.%22%2C%22lastName%22%3A%22Datarwala%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22K.K.%22%2C%22lastName%22%3A%22Bhakat%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S.%22%2C%22lastName%22%3A%22Mitra%22%7D%5D%2C%22abstractNote%22%3A%22Posttranslational%20modifications%20of%20DNA%20repair%20proteins%20have%20been%20linked%20to%20their%20function.%20However%2C%20it%20is%20not%20clear%20if%20posttranslational%20acetylation%20affects%20subcellular%20localization%20of%20these%20enzymes.%20Here%2C%20we%20show%20that%20the%20human%20DNA%20glycosylase%20NEIL1%2C%20which%20is%20involved%20in%20repair%20of%20both%20endo-%20and%20exogenously%20generated%20oxidized%20bases%20via%20the%20base%20excision%20repair%20%28BER%29%20pathway%2C%20is%20acetylated%20by%20histone%20acetyltransferase%20p300.%20Acetylation%20occurs%20predominantly%20at%20Lys%20residues%20296%2C%20297%20and%20298%20located%20in%20NEIL1%5Cu2019s%20disordered%20C-terminal%20domain.%20NEIL1%20mutant%20having%20the%20substitution%20of%20Lys%20296%5Cu2013298%20with%20neutral%20Ala%20loses%20nuclear%20localization%2C%20whereas%20Lys%20%26gt%3B%20Arg%20substitution%20%28in%203KR%20mutant%29%20at%20the%20same%20sites%20does%20not%20affect%20NEIL1%5Cu2019s%20nuclear%20localization%20or%20chromatin%20binding%2C%20presumably%20due%20to%20retention%20of%20the%20positive%20charge.%20Although%20non-acetylated%20NEIL1%20can%20bind%20to%20chromatin%2C%20acetylated%20NEIL1%20is%20exclusively%20chromatin-bound.%20NEIL1%20acetylation%20while%20dispensable%20for%20its%20glycosylase%20activity%20enhances%20it%20due%20to%20increased%20product%20release.%20The%20acetylation-defective%203KR%20mutant%20forms%20less%20stable%20complexes%20with%20various%20chromatin%20proteins%2C%20including%20histone%20chaperones%20and%20BER%5C%2Fsingle-strand%20break%20repair%20partners%2C%20than%20the%20wild-type%20%28WT%29%20NEIL1.%20We%20also%20showed%20that%20the%20repair%20complex%20with%20WT%20NEIL1%20has%20significantly%20higher%20BER%20activity%20than%20the%203KR%20mutant%20complex.%20This%20is%20consistent%20with%20reduced%20resistance%20of%20non-acetylable%20mutant%20NEIL1%20expressing%20cells%20to%20oxidative%20stress%20relative%20to%20cells%20expressing%20the%20acetylable%20WT%20enzyme.%20We%20thus%20conclude%20that%20the%20major%20role%20of%20acetylable%20Lys%20residues%20in%20NEIL1%20is%20to%20stabilize%20the%20formation%20of%20chromatin-bound%20repair%20complexes%20which%20protect%20cells%20from%20oxidative%20stress.%20%5Cu00a9%202018%20Elsevier%20B.V.%22%2C%22date%22%3A%222018%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.1016%5C%2Fj.dnarep.2018.04.001%22%2C%22ISSN%22%3A%22%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22X4LHCUID%22%5D%2C%22dateModified%22%3A%222019-02-04T16%3A53%3A08Z%22%7D%7D%2C%7B%22key%22%3A%224WWG8R6D%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Yang%20et%20al.%22%2C%22parsedDate%22%3A%222017%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BYang%2C%20C.%2C%20%26lt%3Bstrong%26gt%3BSengupta%26lt%3B%5C%2Fstrong%26gt%3B%2C%20S.%2C%20Hegde%2C%20P.%20M.%20et%20al.%20%282017%29.%20Regulation%20of%20oxidized%20base%20damage%20repair%20by%20chromatin%20assembly%20factor%201%20subunit%20A.%20%26lt%3Bi%26gt%3BNucleic%20Acids%20Research%26lt%3B%5C%2Fi%26gt%3B%20%26lt%3Bi%26gt%3B45%26lt%3B%5C%2Fi%26gt%3B%2C%20739%26%23x2013%3B748.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1093%5C%2Fnar%5C%2Fgkw1024%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1093%5C%2Fnar%5C%2Fgkw1024%26lt%3B%5C%2Fa%26gt%3B.%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Regulation%20of%20oxidized%20base%20damage%20repair%20by%20chromatin%20assembly%20factor%201%20subunit%20A%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22C.%22%2C%22lastName%22%3A%22Yang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S.%22%2C%22lastName%22%3A%22Sengupta%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22P.M.%22%2C%22lastName%22%3A%22Hegde%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.%22%2C%22lastName%22%3A%22Mitra%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S.%22%2C%22lastName%22%3A%22Jiang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22B.%22%2C%22lastName%22%3A%22Holey%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.H.%22%2C%22lastName%22%3A%22Sarker%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22M.-S.%22%2C%22lastName%22%3A%22Tsai%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22M.L.%22%2C%22lastName%22%3A%22Hegde%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S.%22%2C%22lastName%22%3A%22Mitra%22%7D%5D%2C%22abstractNote%22%3A%22Reactive%20oxygen%20species%20%28ROS%29%2C%20generated%20both%20endogenously%20and%20in%20response%20to%20exogenous%20stress%2C%20induce%20point%20mutations%20by%20mis-replication%20of%20oxidized%20bases%20and%20other%20lesions%20in%20the%20genome.%20Repair%20of%20these%20lesions%20via%20base%20excision%20repair%20%28BER%29%20pathway%20maintains%20genomic%20fidelity.%20Regulation%20of%20the%20BER%20pathway%20for%20mutagenic%20oxidized%20bases%2C%20initiated%20by%20NEIL1%20and%20other%20DNA%20glycosylases%20at%20the%20chromatin%20level%20remains%20unexplored.%20Whether%20single%20nucleotide%20%28SN%29-BER%20of%20a%20damaged%20base%20requires%20histone%20deposition%20or%20nucleosome%20remodeling%20is%20unknown%2C%20unlike%20nucleosome%20reassembly%20which%20is%20shown%20to%20be%20required%20for%20other%20DNA%20repair%20processes.%20Here%20we%20show%20that%20chromatin%20assembly%20factor%20%28CAF%29-1%20subunit%20A%20%28CHAF1A%29%2C%20the%20p150%20subunit%20of%20the%20histone%20H3%5C%2FH4%20chaperone%2C%20and%20its%20partner%20anti-silencing%20function%20protein%201A%20%28ASF1A%29%2C%20which%20we%20identified%20in%20human%20NEIL1%20immunoprecipitation%20complex%2C%20transiently%20dissociate%20from%20chromatin%20bound%20NEIL1%20complex%20in%20G1%20cells%20after%20induction%20of%20oxidative%20base%20damage.%20CHAF1A%20inhibits%20NEIL1%20initiated%20repair%20in%20vitro.%20Subsequent%20restoration%20of%20the%20chaperone-BER%20complex%20in%20cell%2C%20presumably%20after%20completion%20of%20repair%2C%20suggests%20that%20histone%20chaperones%20sequester%20the%20repair%20complex%20for%20oxidized%20bases%20in%20non-replicating%20chromatin%2C%20and%20allow%20repair%20when%20oxidized%20bases%20are%20induced%20in%20the%20genome.%20%5Cu00a9%20The%20Author%28s%29%202016.%20Published%20by%20Oxford%20University%20Press%20on%20behalf%20of%20Nucleic%20Acids%20Research.%22%2C%22date%22%3A%222017%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.1093%5C%2Fnar%5C%2Fgkw1024%22%2C%22ISSN%22%3A%22%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22X4LHCUID%22%5D%2C%22dateModified%22%3A%222019-03-06T16%3A29%3A22Z%22%7D%7D%2C%7B%22key%22%3A%22JVT6WG2T%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Vasquez%20et%20al.%22%2C%22parsedDate%22%3A%222017%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BVasquez%2C%20V.%2C%20Mitra%2C%20J.%2C%20Hegde%2C%20P.%20M.%20et%20al.%20%282017%29.%20Chromatin-Bound%20Oxidized%20%26%23x3B1%3B-Synuclein%20Causes%20Strand%20Breaks%20in%20Neuronal%20Genomes%20in%20in%20vitro%20Models%20of%20Parkinson%26%23x2019%3Bs%20Disease.%20%26lt%3Bi%26gt%3BJournal%20of%20Alzheimer%26%23x2019%3Bs%20Disease%26lt%3B%5C%2Fi%26gt%3B%20%26lt%3Bi%26gt%3B60%26lt%3B%5C%2Fi%26gt%3B%2C%20S133%26%23x2013%3BS150.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.3233%5C%2FJAD-170342%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.3233%5C%2FJAD-170342%26lt%3B%5C%2Fa%26gt%3B.%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Chromatin-Bound%20Oxidized%20%5Cu03b1-Synuclein%20Causes%20Strand%20Breaks%20in%20Neuronal%20Genomes%20in%20in%20vitro%20Models%20of%20Parkinson%27s%20Disease%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22V.%22%2C%22lastName%22%3A%22Vasquez%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.%22%2C%22lastName%22%3A%22Mitra%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22P.M.%22%2C%22lastName%22%3A%22Hegde%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%22%2C%22lastName%22%3A%22Pandey%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S.%22%2C%22lastName%22%3A%22Sengupta%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S.%22%2C%22lastName%22%3A%22Mitra%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22K.S.%22%2C%22lastName%22%3A%22Rao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22M.L.%22%2C%22lastName%22%3A%22Hegde%22%7D%5D%2C%22abstractNote%22%3A%22Alpha-synuclein%20%28%5Cu03b1-Syn%29%20overexpression%20and%20misfolding%5C%2Faggregation%20in%20degenerating%20dopaminergic%20neurons%20have%20long%20been%20implicated%20in%20Parkinson%26%23039%3Bs%20disease%20%28PD%29.%20The%20neurotoxicity%20of%20%5Cu03b1-Syn%20is%20enhanced%20by%20iron%20%28Fe%29%20and%20other%20pro-oxidant%20metals%2C%20leading%20to%20generation%20of%20reactive%20oxygen%20species%20in%20PD%20brain.%20Although%20%5Cu03b1-Syn%20is%20predominantly%20localized%20in%20presynaptic%20nerve%20terminals%2C%20a%20small%20fraction%20exists%20in%20neuronal%20nuclei.%20However%2C%20the%20functional%20and%5C%2For%20pathological%20role%20of%20nuclear%20%5Cu03b1-Syn%20is%20unclear.%20Following%20up%20on%20our%20earlier%20report%20that%20%5Cu03b1-Syn%20directly%20binds%20DNA%20in%20vitro%2C%20here%20we%20confirm%20the%20nuclear%20localization%20and%20chromatin%20association%20of%20%5Cu03b1-Syn%20in%20neurons%20using%20proximity%20ligation%20and%20chromatin%20immunoprecipitation%20analysis.%20Moderate%20%28%5Cu223c2-fold%29%20increase%20in%20%5Cu03b1-Syn%20expression%20in%20neural%20lineage%20progenitor%20cells%20%28NPC%29%20derived%20from%20induced%20pluripotent%20human%20stem%20cells%20%28iPSCs%29%20or%20differentiated%20SHSY-5Y%20cells%20caused%20DNA%20strand%20breaks%20in%20the%20nuclear%20genome%2C%20which%20was%20further%20enhanced%20synergistically%20by%20Fe%20salts.%20Furthermore%2C%20%5Cu03b1-Syn%20required%20nuclear%20localization%20for%20inducing%20genome%20damage%20as%20revealed%20by%20the%20effect%20of%20nucleus%20versus%20cytosol-specific%20mutants.%20Enhanced%20DNA%20damage%20by%20oxidized%20and%20misfolded%5C%2Foligomeric%20%5Cu03b1-Syn%20suggests%20that%20DNA%20nicking%20activity%20is%20mediated%20by%20the%20chemical%20nuclease%20activity%20of%20an%20oxidized%20peptide%20segment%20in%20the%20misfolded%20%5Cu03b1-Syn.%20Consistent%20with%20this%20finding%2C%20a%20marked%20increase%20in%20Fe-dependent%20DNA%20breaks%20was%20observed%20in%20NPCs%20from%20a%20PD%20patient-derived%20iPSC%20line%20harboring%20triplication%20of%20the%20SNCA%20gene.%20Finally%2C%20%5Cu03b1-Syn%20combined%20with%20Fe%20significantly%20promoted%20neuronal%20cell%20death.%20Together%2C%20these%20findings%20provide%20a%20novel%20molecular%20insight%20into%20the%20direct%20role%20of%20%5Cu03b1-Syn%20in%20inducing%20neuronal%20genome%20damage%2C%20which%20could%20possibly%20contribute%20to%20neurodegeneration%20in%20PD.%20%5Cu00a9%202017%20-%20IOS%20Press%20and%20the%20authors.%20All%20rights%20reserved.%22%2C%22date%22%3A%222017%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.3233%5C%2FJAD-170342%22%2C%22ISSN%22%3A%22%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22X4LHCUID%22%5D%2C%22dateModified%22%3A%222019-02-04T16%3A53%3A08Z%22%7D%7D%2C%7B%22key%22%3A%22W5BLPQQ3%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Roychoudhury%20et%20al.%22%2C%22parsedDate%22%3A%222017%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BRoychoudhury%2C%20S.%2C%20Nath%2C%20S.%2C%20Song%2C%20H.%20et%20al.%20%282017%29.%20Human%20apurinic%5C%2Fapyrimidinic%20endonuclease%20%28APE1%29%20is%20acetylated%20at%20DNA%20damage%20sites%20in%20chromatin%2C%20and%20acetylation%20modulates%20its%20DNA%20repair%20activity.%20%26lt%3Bi%26gt%3BMolecular%20and%20Cellular%20Biology%26lt%3B%5C%2Fi%26gt%3B%20%26lt%3Bi%26gt%3B37%26lt%3B%5C%2Fi%26gt%3B.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1128%5C%2FMCB.00401-16%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1128%5C%2FMCB.00401-16%26lt%3B%5C%2Fa%26gt%3B.%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Human%20apurinic%5C%2Fapyrimidinic%20endonuclease%20%28APE1%29%20is%20acetylated%20at%20DNA%20damage%20sites%20in%20chromatin%2C%20and%20acetylation%20modulates%20its%20DNA%20repair%20activity%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S.%22%2C%22lastName%22%3A%22Roychoudhury%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S.%22%2C%22lastName%22%3A%22Nath%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22H.%22%2C%22lastName%22%3A%22Song%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22M.L.%22%2C%22lastName%22%3A%22Hegde%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22L.J.%22%2C%22lastName%22%3A%22Bellot%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.K.%22%2C%22lastName%22%3A%22Mantha%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S.%22%2C%22lastName%22%3A%22Sengupta%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S.%22%2C%22lastName%22%3A%22Ray%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%22%2C%22lastName%22%3A%22Natarajan%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22K.K.%22%2C%22lastName%22%3A%22Bhakat%22%7D%5D%2C%22abstractNote%22%3A%22Apurinic%5C%2Fapyrimidinic%20%28AP%29%20sites%2C%20the%20most%20frequently%20formed%20DNA%20lesions%20in%20the%20genome%2C%20inhibit%20transcription%20and%20block%20replication.%20The%20primary%20enzyme%20that%20repairs%20AP%20sites%20in%20mammalian%20cells%20is%20the%20AP%20endonuclease%20%28APE1%29%2C%20which%20functions%20through%20the%20base%20excision%20repair%20%28BER%29%20pathway.%20Although%20the%20mechanism%20by%20which%20APE1%20repairs%20AP%20sites%20in%20vitro%20has%20been%20extensively%20investigated%2C%20it%20is%20largely%20unknown%20how%20APE1%20repairs%20AP%20sites%20in%20cells.%20Here%2C%20we%20show%20that%20APE1%20is%20acetylated%20%28AcAPE1%29%20after%20binding%20to%20the%20AP%20sites%20in%20chromatin%20and%20that%20AcAPE1%20is%20exclusively%20present%20on%20chromatin%20throughout%20the%20cell%20cycle.%20Positive%20charges%20of%20acetylable%20lysine%20residues%20in%20the%20N-terminal%20domain%20of%20APE1%20are%20essential%20for%20chromatin%20association.%20Acetylation-mediated%20neutralization%20of%20the%20positive%20charges%20of%20the%20lysine%20residues%20in%20the%20N-terminal%20domain%20of%20APE1%20induces%20a%20conformational%20change%3B%20this%20in%20turn%20enhances%20the%20AP%20endonuclease%20activity%20of%20APE1.%20In%20the%20absence%20of%20APE1%20acetylation%2C%20cells%20accumulated%20AP%20sites%20in%20the%20genome%20and%20showed%20higher%20sensitivity%20to%20DNA-damaging%20agents.%20Thus%2C%20mammalian%20cells%2C%20unlike%20Saccharomyces%20cerevisiae%20or%20Escherichia%20coli%20cells%2C%20require%20acetylation%20of%20APE1%20for%20the%20efficient%20repair%20of%20AP%20sites%20and%20base%20damage%20in%20the%20genome.%20Our%20study%20reveals%20that%20APE1%20acetylation%20is%20an%20integral%20part%20of%20the%20BER%20pathway%20for%20maintaining%20genomic%20integrity.%20%5Cu00a9%202017%20Roychoudhury%20et%20al.%22%2C%22date%22%3A%222017%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.1128%5C%2FMCB.00401-16%22%2C%22ISSN%22%3A%22%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22X4LHCUID%22%5D%2C%22dateModified%22%3A%222019-02-04T16%3A53%3A08Z%22%7D%7D%2C%7B%22key%22%3A%22DB7ZBEC8%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Dutta%20et%20al.%22%2C%22parsedDate%22%3A%222017%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BDutta%2C%20A.%2C%20Eckelmann%2C%20B.%2C%20Adhikari%2C%20S.%20et%20al.%20%282017%29.%20Microhomology-mediated%20end%20joining%20is%20activated%20in%20irradiated%20human%20cells%20due%20to%20phosphorylation-dependent%20formation%20of%20the%20XRCC1%20repair%20complex.%20%26lt%3Bi%26gt%3BNucleic%20Acids%20Research%26lt%3B%5C%2Fi%26gt%3B%20%26lt%3Bi%26gt%3B45%26lt%3B%5C%2Fi%26gt%3B%2C%202585%26%23x2013%3B2599.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1093%5C%2Fnar%5C%2Fgkw1262%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1093%5C%2Fnar%5C%2Fgkw1262%26lt%3B%5C%2Fa%26gt%3B.%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Microhomology-mediated%20end%20joining%20is%20activated%20in%20irradiated%20human%20cells%20due%20to%20phosphorylation-dependent%20formation%20of%20the%20XRCC1%20repair%20complex%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%22%2C%22lastName%22%3A%22Dutta%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22B.%22%2C%22lastName%22%3A%22Eckelmann%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S.%22%2C%22lastName%22%3A%22Adhikari%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22K.M.%22%2C%22lastName%22%3A%22Ahmed%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S.%22%2C%22lastName%22%3A%22Sengupta%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%22%2C%22lastName%22%3A%22Pandey%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22P.M.%22%2C%22lastName%22%3A%22Hegde%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22M.-S.%22%2C%22lastName%22%3A%22Tsai%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.A.%22%2C%22lastName%22%3A%22Tainer%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22M.%22%2C%22lastName%22%3A%22Weinfeld%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22M.L.%22%2C%22lastName%22%3A%22Hegde%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S.%22%2C%22lastName%22%3A%22Mitra%22%7D%5D%2C%22abstractNote%22%3A%22Microhomology-mediated%20end%20joining%20%28MMEJ%29%2C%20an%20error-prone%20pathway%20for%20DNA%20double-strand%20break%20%28DSB%29%20repair%2C%20is%20implicated%20in%20genomic%20rearrangement%20and%20oncogenic%20transformation%3B%20however%2C%20its%20contribution%20to%20repair%20of%20radiation-induced%20DSBs%20has%20not%20been%20characterized.%20We%20used%20recircularization%20of%20a%20linearized%20plasmid%20with%203%5Cu00a9-P-blocked%20termini%2C%20mimicking%20those%20at%20X-ray-induced%20strand%20breaks%2C%20to%20recapitulate%20DSB%20repair%20via%20MMEJ%20or%20nonhomologous%20end-joining%20%28NHEJ%29.%20Sequence%20analysis%20of%20the%20circularized%20plasmids%20allowedmeasurement%20of%20relative%20activity%20of%20MMEJ%20versus%20NHEJ.%20While%20we%20predictably%20observed%20NHEJ%20to%20be%20the%20predominant%20pathway%20for%20DSB%20repair%20in%20our%20assay%2C%20MMEJ%20was%20significantly%20enhanced%20in%20preirradiated%20cells%2C%20independent%20of%20their%20radiation-induced%20arrest%20in%20the%20G2%5C%2FM%20phase.%20MMEJ%20activation%20was%20dependent%20on%20XRCC1%20phosphorylation%20by%20casein%20kinase%202%20%28CK2%29%2C%20enhancing%20XRCC1%26%23039%3Bs%20interaction%20with%20the%20end%20resection%20enzymes%20MRE11%20and%20CtIP.%20Both%20endonuclease%20and%20exonuclease%20activities%20of%20MRE11%20were%20required%20for%20MMEJ%2C%20as%20has%20been%20observed%20for%20homology-directed%20DSB%20repair%20%28HDR%29.%20Furthermore%2C%20the%20XRCC1%20co-immunoprecipitate%20complex%20%28IP%29%20displayed%20MMEJ%20activity%20in%20vitro%2C%20which%20was%20significantly%20elevated%20after%20irradiation.%20Our%20studies%20thus%20suggest%20that%20radiation-mediated%20enhancement%20of%20MMEJ%20in%20cells%20surviving%20radiation%20therapy%20may%20contribute%20to%20their%20radioresistance%20and%20could%20be%20therapeutically%20targeted.%20%5Cu00a9%20The%20Author%28s%29%202016.%22%2C%22date%22%3A%222017%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.1093%5C%2Fnar%5C%2Fgkw1262%22%2C%22ISSN%22%3A%22%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22X4LHCUID%22%5D%2C%22dateModified%22%3A%222019-02-04T16%3A53%3A08Z%22%7D%7D%2C%7B%22key%22%3A%22XH7CATWP%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Bhakat%20et%20al.%22%2C%22parsedDate%22%3A%222016%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BBhakat%2C%20K.%20K.%2C%20%26lt%3Bstrong%26gt%3BSengupta%26lt%3B%5C%2Fstrong%26gt%3B%2C%20S.%2C%20Adeniyi%2C%20V.%20F.%20et%20al.%20%282016%29.%20Regulation%20of%20limited%20N-terminal%20proteolysis%20of%20APE1%20in%20tumor%20via%20acetylation%20and%20its%20role%20in%20cell%20proliferation.%20%26lt%3Bi%26gt%3BOncotarget%26lt%3B%5C%2Fi%26gt%3B%20%26lt%3Bi%26gt%3B7%26lt%3B%5C%2Fi%26gt%3B%2C%2022590%26%23x2013%3B22604.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.18632%5C%2Foncotarget.8026%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.18632%5C%2Foncotarget.8026%26lt%3B%5C%2Fa%26gt%3B.%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Regulation%20of%20limited%20N-terminal%20proteolysis%20of%20APE1%20in%20tumor%20via%20acetylation%20and%20its%20role%20in%20cell%20proliferation%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22K.K.%22%2C%22lastName%22%3A%22Bhakat%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S.%22%2C%22lastName%22%3A%22Sengupta%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22V.F.%22%2C%22lastName%22%3A%22Adeniyi%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S.%22%2C%22lastName%22%3A%22Roychoudhury%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S.%22%2C%22lastName%22%3A%22Nath%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22L.J.%22%2C%22lastName%22%3A%22Bellot%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22D.%22%2C%22lastName%22%3A%22Feng%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.K.%22%2C%22lastName%22%3A%22Mantha%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22M.%22%2C%22lastName%22%3A%22Sinha%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S.%22%2C%22lastName%22%3A%22Qiu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22B.A.%22%2C%22lastName%22%3A%22Luxon%22%7D%5D%2C%22abstractNote%22%3A%22Mammalian%20apurinic%5C%2Fapyrimidinic%20%28AP%29%20endonuclease%201%20%28APE1%29%2C%20a%20ubiquitous%20and%20multifunctional%20protein%2C%20plays%20an%20essential%20role%20in%20the%20repair%20of%20both%20endogenous%20and%20drug-induced%20DNA%20damages%20in%20the%20genome.%20Unlike%20its%20E.coli%20counterpart%20Xth%2C%20mammalian%20APE1%20has%20a%20unique%20N-terminal%20domain%20and%20possesses%20both%20DNA%20damage%20repair%20and%20transcriptional%20regulatory%20functions.%20Although%20the%20overexpression%20of%20APE1%20in%20diverse%20cancer%20types%20and%20the%20association%20of%20APE1%20expression%20with%20chemotherapy%20resistance%20and%20poor%20prognosis%20are%20well%20documented%2C%20the%20cellular%20and%20molecular%20mechanisms%20that%20alter%20APE1%20functions%20during%20tumorigenesis%20are%20largely%20unknown.%20Here%2C%20we%20show%20the%20presence%20of%20full-length%20APE1%20and%20N-terminal%20truncated%20isoforms%20of%20APE1%20in%20tumor%20tissue%20samples%20of%20various%20cancer%20types.%20However%2C%20primary%20tumor%20tissue%20has%20higher%20levels%20of%20acetylated%20APE1%20%28AcAPE1%29%20as%20well%20as%20full-length%20APE1%20compared%20to%20adjacent%20non-tumor%20tissue.%20We%20found%20that%20APE1%20is%20proteolytically%20cleaved%20by%20an%20unknown%20serine%20protease%20at%20its%20N-terminus%20following%20residue%20lysine%20%28Lys%29%20Lys6%20and%5C%2For%20Lys7%20and%20after%20Lys27%20and%20Lys31%20or%20Lys32.%20Acetylation%20of%20these%20Lys%20residues%20in%20APE1%20prevents%20this%20proteolysis.%20The%20N-terminal%20domain%20of%20APE1%20and%20its%20acetylation%20are%20required%20for%20modulation%20of%20the%20expression%20of%20hundreds%20of%20genes.%20Importantly%2C%20we%20found%20that%20AcAPE1%20is%20essential%20for%20sustained%20cell%20proliferation.%20Together%2C%20our%20study%20demonstrates%20that%20increased%20acetylation%20levels%20of%20APE1%20in%20tumor%20cells%20inhibit%20the%20limited%20N-terminal%20proteolysis%20of%20APE1%20and%20thereby%20maintain%20the%20functions%20of%20APE1%20to%20promote%20tumor%20cells%26%23039%3B%20sustained%20proliferation%20and%20survival.%22%2C%22date%22%3A%222016%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.18632%5C%2Foncotarget.8026%22%2C%22ISSN%22%3A%22%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22X4LHCUID%22%5D%2C%22dateModified%22%3A%222020-10-07T22%3A39%3A48Z%22%7D%7D%5D%7D
Bacolla, A., Sengupta, S., Ye, Z. et al. (2021). Heritable pattern of oxidized DNA base repair coincides with pre-targeting of repair complexes to open chromatin. Nucleic Acids Res 49, 221–243. https://doi.org/10.1093/nar/gkaa1120.
Sengupta, S., Wang, H., Yang, C. et al. (2020). Ligand-induced gene activation is associated with oxidative genome damage whose repair is required for transcription. Proc Natl Acad Sci U S A 117, 22183–22192. https://doi.org/10.1073/pnas.1919445117.
Bhakat, K. K., Sengupta, S. and Mitra, S. (2020). Fine-tuning of DNA base excision/strand break repair via acetylation. DNA Repair (Amst) 93, 102931. https://doi.org/10.1016/j.dnarep.2020.102931.
Sengupta, S., Yang, C., Eckelmann, B. J. et al. (2018). Regulation of Oxidized Base Repair in Human Chromatin by Posttranslational Modification. In Advances in DNA Repair. Available at: https://www.intechopen.com/online-first/regulation-of-oxidized-base-repair-in-human-chromatin-by-posttranslational-modification [Accessed February 6, 2019].
Sengupta, S., Yang, C., Hegde, M. L. et al. (2018). Acetylation of oxidized base repair-initiating NEIL1 DNA glycosylase required for chromatin-bound repair complex formation in the human genome increases cellular resistance to oxidative stress. DNA Repair 66–67, 1–10. https://doi.org/10.1016/j.dnarep.2018.04.001.
Yang, C., Sengupta, S., Hegde, P. M. et al. (2017). Regulation of oxidized base damage repair by chromatin assembly factor 1 subunit A. Nucleic Acids Research 45, 739–748. https://doi.org/10.1093/nar/gkw1024.
Vasquez, V., Mitra, J., Hegde, P. M. et al. (2017). Chromatin-Bound Oxidized α-Synuclein Causes Strand Breaks in Neuronal Genomes in in vitro Models of Parkinson’s Disease. Journal of Alzheimer’s Disease 60, S133–S150. https://doi.org/10.3233/JAD-170342.
Roychoudhury, S., Nath, S., Song, H. et al. (2017). Human apurinic/apyrimidinic endonuclease (APE1) is acetylated at DNA damage sites in chromatin, and acetylation modulates its DNA repair activity. Molecular and Cellular Biology 37. https://doi.org/10.1128/MCB.00401-16.
Dutta, A., Eckelmann, B., Adhikari, S. et al. (2017). Microhomology-mediated end joining is activated in irradiated human cells due to phosphorylation-dependent formation of the XRCC1 repair complex. Nucleic Acids Research 45, 2585–2599. https://doi.org/10.1093/nar/gkw1262.
Bhakat, K. K., Sengupta, S., Adeniyi, V. F. et al. (2016). Regulation of limited N-terminal proteolysis of APE1 in tumor via acetylation and its role in cell proliferation. Oncotarget 7, 22590–22604. https://doi.org/10.18632/oncotarget.8026.