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Article: ATM-dependent phosphorylation of the Fanconi anemia protein PALB2 promotes the DNA Damage Response

TitleATM-dependent phosphorylation of the Fanconi anemia protein PALB2 promotes the DNA Damage Response
Authors
KeywordsBRCA1
DNA damage
DNA damage response
Phosphorylation
Protein phosphorylation
Issue Date2015
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal of Biological Chemistry, 2015, v. 290 n. 46, p. 27545-27556 How to Cite?
AbstractThe Fanconi anemia protein PALB2, also known as FANCN, protects genome integrity by regulating DNA repair and cell cycle checkpoints. Exactly how PALB2 functions may be temporally coupled with detection and signaling of DNA damage is not known. Intriguingly, we found that PALB2 is transformed into a hyperphosphorylated state in response to ionizing radiation (IR). IR treatment specifically triggered PALB2 phosphorylation at Ser-157 and Ser-376 in manners that required the master DNA damage response kinase Ataxia telangiectasia mutated, revealing potential mechanistic links between PALB2 and the Ataxia telangiectasia mutated-dependent DNA damage responses. Consistently, dysregulated PALB2 phosphorylation resulted in sustained activation of DDRs. Full-blown PALB2 phosphorylation also required the breast and ovarian susceptible gene product BRCA1, highlighting important roles of the BRCA1-PALB2 interaction in orchestrating cellular responses to genotoxic stress. In summary, our phosphorylation analysis of tumor suppressor protein PALB2 uncovers new layers of regulatory mechanisms in the maintenance of genome stability and tumor suppression.
Persistent Identifierhttp://hdl.handle.net/10722/228958
ISSN
2020 Impact Factor: 5.157
2023 SCImago Journal Rankings: 1.766
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorGuo, Y-
dc.contributor.authorFeng, W-
dc.contributor.authorSy, MH-
dc.contributor.authorHuen, MSY-
dc.date.accessioned2016-08-23T14:08:05Z-
dc.date.available2016-08-23T14:08:05Z-
dc.date.issued2015-
dc.identifier.citationJournal of Biological Chemistry, 2015, v. 290 n. 46, p. 27545-27556-
dc.identifier.issn0021-9258-
dc.identifier.urihttp://hdl.handle.net/10722/228958-
dc.description.abstractThe Fanconi anemia protein PALB2, also known as FANCN, protects genome integrity by regulating DNA repair and cell cycle checkpoints. Exactly how PALB2 functions may be temporally coupled with detection and signaling of DNA damage is not known. Intriguingly, we found that PALB2 is transformed into a hyperphosphorylated state in response to ionizing radiation (IR). IR treatment specifically triggered PALB2 phosphorylation at Ser-157 and Ser-376 in manners that required the master DNA damage response kinase Ataxia telangiectasia mutated, revealing potential mechanistic links between PALB2 and the Ataxia telangiectasia mutated-dependent DNA damage responses. Consistently, dysregulated PALB2 phosphorylation resulted in sustained activation of DDRs. Full-blown PALB2 phosphorylation also required the breast and ovarian susceptible gene product BRCA1, highlighting important roles of the BRCA1-PALB2 interaction in orchestrating cellular responses to genotoxic stress. In summary, our phosphorylation analysis of tumor suppressor protein PALB2 uncovers new layers of regulatory mechanisms in the maintenance of genome stability and tumor suppression.-
dc.languageeng-
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/-
dc.relation.ispartofJournal of Biological Chemistry-
dc.subjectBRCA1-
dc.subjectDNA damage-
dc.subjectDNA damage response-
dc.subjectPhosphorylation-
dc.subjectProtein phosphorylation-
dc.titleATM-dependent phosphorylation of the Fanconi anemia protein PALB2 promotes the DNA Damage Response-
dc.typeArticle-
dc.identifier.emailFeng, W: fengwj83@hku.hk-
dc.identifier.emailSy, MH: mhsy@hku.hk-
dc.identifier.emailHuen, MSY: huen.michael@hku.hk-
dc.identifier.authorityHuen, MSY=rp01336-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1074/jbc.M115.672626-
dc.identifier.pmid26420486-
dc.identifier.pmcidPMC4646007-
dc.identifier.scopuseid_2-s2.0-84946919323-
dc.identifier.hkuros262609-
dc.identifier.volume290-
dc.identifier.issue46-
dc.identifier.spage27545-
dc.identifier.epage27556-
dc.identifier.isiWOS:000365757500011-
dc.publisher.placeUnited States-
dc.identifier.issnl0021-9258-

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