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dc.contributor.authorSengupta, S.
dc.contributor.authorMantha, Anil K.
dc.contributor.authorSong, H.
dc.contributor.authorRoychoudhury, S.
dc.contributor.authorNath, S.
dc.contributor.authorRay, S.
dc.contributor.authorBhakat, K.K.
dc.date.accessioned2013-01-11T15:18:23Z
dc.date.available2013-01-11T15:18:23Z
dc.date.issued2016
dc.date.issued2016
dc.identifier.citationSengupta, S., Mantha, A. K., Song, H., Roychoudhury, S., Nath, S., Ray, S., & Bhakat, K. K. (2016). Elevated level of acetylation of APE1 in tumor cells modulates DNA damage repair. Oncotarget, 7(46), 75197-75209. doi: 10.18632/oncotarget.12113en_US
dc.identifier.issnOnline- 1949-2553
dc.identifier.issn19492553
dc.identifier.urihttp://210.212.34.21/handle/32116/386
dc.description.abstractApurinic/apyrimidinic (AP) sites are frequently generated in the genome by spontaneous depurination/depyrimidination or after removal of oxidized/modified bases by DNA glycosylases during the base excision repair (BER) pathway. Unrepaired AP sites are mutagenic and block DNA replication and transcription. The primary enzyme to repair AP sites in mammalian cells is AP endonuclease (APE1), which plays a key role in this repair pathway. Although overexpression of APE1 in diverse cancer types and its association with chemotherapeutic resistance are well documented, alteration of posttranslational modification of APE1 and modulation of its functions during tumorigenesis are largely unknown. Here, we show that both classical histone deacetylase HDAC1 and NAD+-dependent deacetylase SIRT1 regulate acetylation level of APE1 and acetylation of APE1 enhances its AP-endonuclease activity both in vitro and in cells. Modulation of APE1 acetylation level in cells alters AP site repair capacity of the cell extracts in vitro. Primary tumor tissues of diverse cancer types have higher level of acetylated APE1 (AcAPE1) compared to adjacent non-tumor tissue and exhibit enhanced AP site repair capacity. Importantly, in the absence of APE1 acetylation, cells accumulate AP sites in the genome and show increased sensitivity to DNA damaging agents. Together, our study demonstrates that elevation of acetylation level of APE1 in tumor could be a novel mechanism by which cells handle the elevated levels of DNA damages in response to genotoxic stress and maintain sustained proliferation.en_US
dc.language.isoenen_US
dc.publisherImpact Journals LLCen_US
dc.subjectApurinic Endonuclease 1en_US
dc.subjectEndonucleaseen_US
dc.subjectHistone Deacetylase 1en_US
dc.subjectNicotinamide Adenine Dinucleotideen_US
dc.subjectSirtuin 1en_US
dc.subjectUnclassified Drugen_US
dc.subjectApex1 Protein, Humanen_US
dc.subjectDna (Apurinic Or Apyrimidinic Site) Lyaseen_US
dc.subjectHistone Deacetylase 1en_US
dc.subjectNicotinamide Adenine Dinucleotideen_US
dc.subjectProtein Bindingen_US
dc.subjectSirtuin 1 Bioaccumulationen_US
dc.subjectCell Proliferationen_US
dc.subjectCell Survivalen_US
dc.subjectControlled Studyen_US
dc.subjectDeacetylationen_US
dc.subjectDna Repairen_US
dc.subjectEmbryoen_US
dc.subjectEnzyme Activityen_US
dc.subjectGenotoxicityen_US
dc.subjectHumanen_US
dc.subjectHuman Cellen_US
dc.subjectHuman Tissueen_US
dc.subjectIn Vitro Studyen_US
dc.subjectProtein Acetylationen_US
dc.subjectProteinen_US
dc.titleElevated level of acetylation of APE1 in tumor cells modulates DNA damage repairen_US
dc.typeArticleen_US
dc.identifier.doi10.18632/oncotarget.12113
dc.identifier.urlhttp://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=12113&path[]=38331
dc.title.journalOncotarget


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