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dc.contributor.authorFan, L.
dc.contributor.authorXu, S.
dc.contributor.authorZhang, F.
dc.contributor.authorCui, X.
dc.contributor.authorClark, D.J.
dc.contributor.authorYang, A.
dc.contributor.authorHussain, A.
dc.contributor.authorRassool, F.
dc.contributor.authorQi, J.
dc.date.accessioned2020-04-14T14:28:48Z
dc.date.available2020-04-14T14:28:48Z
dc.date.issued2020
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85082790577&doi=10.1038%2fs41419-020-2405-4&partnerID=40&md5=bede8e0aaf6c59de4d012601769693eb
dc.identifier.urihttp://hdl.handle.net/10713/12542
dc.description.abstractThe DNA damage response (DDR) pathway is a promising target for anticancer therapies. The androgen receptor and myeloblastosis transcription factors have been reported to regulate expression of an overlapping set of DDR genes in prostate cancer cells. Here, we found that histone demethylase JMJD1A regulates expression of a different set of DDR genes largely through c-Myc. Inhibition of JMJD1A delayed the resolution of γ-H2AX foci, reduced the formation of foci containing ubiquitin, 53BP1, BRCA1 or Rad51, and inhibited the reporter activity of double-strand break (DSB) repair. Mechanistically, JMJD1A regulated expression of DDR genes by increasing not only the level but also the chromatin recruitment of c-Myc through H3K9 demethylation. Further, we found that ubiquitin ligase HUWE1 induced the K27-/K29-linked noncanonical ubiquitination of JMJD1A at lysine-918. Ablation of the JMJD1A noncanonical ubiquitination lowered DDR gene expression, impaired DSB repair, and sensitized response of prostate cells to irradiation, topoisomerase inhibitors or PARP inhibitors. Thus, development of agents that target JMJD1A or its noncanonical ubiquitination may sensitize the response of prostate cancer to radiotherapy and possibly also genotoxic therapy. Copyright 2020, The Author(s).en_US
dc.description.sponsorshipThis study is supported by NCI grant R01CA207118 and a V Scholar award (to J.Q.). Part of A.H.'s time was supported by a Merit Review Award (I01 BX000545), Medical Research Service, Department of Veterans Affairs.en_US
dc.description.urihttps://doi.org/10.1038/s41419-020-2405-4en_US
dc.language.isoen_USen_US
dc.publisherSpringer Natureen_US
dc.relation.ispartofCell Death and Disease
dc.subject.lcshProstrate--Canceren_US
dc.subject.meshTranscription Factorsen_US
dc.titleHistone demethylase JMJD1A promotes expression of DNA repair factors and radio-resistance of prostate cancer cellsen_US
dc.typeArticleen_US
dc.identifier.doi10.1038/s41419-020-2405-4
dc.identifier.pmid32238799


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