Distinct functions of Nijmegen breakage syndrome in ataxia telangiectasia mutated-dependent responses to DNA damage

Cited 52 time in webofscience Cited 0 time in scopus
  • Hit : 732
  • Download : 1085
DC FieldValueLanguage
dc.contributor.authorLee, Joo Hyeonko
dc.contributor.authorXu, Boko
dc.contributor.authorLee, Chang-Hunko
dc.contributor.authorAhn, Jun-Youngko
dc.contributor.authorSong, Min Supko
dc.contributor.authorLee, Hoko
dc.contributor.authorCanman, Christine E.ko
dc.contributor.authorLee, Jong-Sooko
dc.contributor.authorKastan, Michael B.ko
dc.contributor.authorLim, Dae-Sikko
dc.date.accessioned2008-06-18T07:19:31Z-
dc.date.available2008-06-18T07:19:31Z-
dc.date.created2012-02-06-
dc.date.created2012-02-06-
dc.date.issued2003-07-
dc.identifier.citationMOLECULAR CANCER RESEARCH, v.1, no.9, pp.674 - 681-
dc.identifier.issn1541-7786-
dc.identifier.urihttp://hdl.handle.net/10203/5162-
dc.description.abstractPhosphorylation of NBS1, the product of the gene mutated in Nijmegen breakage syndrome (NBS), by ataxia telangiectasia mutated (ATM), the product of the gene mutated in ataxia telangiectasia, is required for activation of the S phase checkpoint in response to ionizing radiation (IR). However, NBS1 is also thought to play additional roles in the cellular response to DNA damage. To clarify these additional functions of NBS1, we generated NBS cell lines stably expressing various NBS1 mutants from retroviral vectors. The ATM-dependent activation of CHK2 by IR was defective in NBS cells but was restored by ectopic expression of wild-type NBS1. The defects in ATM-dependent activation of CHK2, S phase checkpoint control, IR-induced nuclear focus formation, and radiation sensitivity apparent in NBS cells were not corrected by expression of NBS1 mutants that lack an intact MRE11 binding domain, suggesting that formation of the NBS1-MRE11-RAD50 complex is required for the corresponding normal phenotypes. Expression of NBS1 proteins with mutated ATM-targeted phosphorylation sites (serines 278 or 343) did not restore S phase checkpoint control but did restore the ability of IR to activate CHK2 and to induce nuclear focus formation and normalized the radiation sensitivity of NBS cells. Expression of NBS1 containing mutations in the forkhead-associated or BRCA1 COOH terminus domains did not correct the defects in radiation sensitivity or nuclear focus formation but did restore S phase checkpoint control in NBS cells. Together, these data demonstrate that multiple functional domains of NBS1 are required for ATM-dependent activation of CHK2, nuclear focus formation, S phase checkpoint control, and cell survival after exposure to IR.-
dc.description.sponsorshipKRF2001-015DS0058 from the Korea Research Foundation; grant CA71387 from the National Cancer Institute; 21st Century Frontier Functional Human Genome Project and Biomedical Research Program of KISTEP (Ministry of Science and Technology of Korea)en
dc.languageEnglish-
dc.language.isoen_USen
dc.publisherAMER ASSOC CANCER RESEARCH-
dc.subjectDOUBLE-STRAND BREAKS-
dc.subjectS-PHASE CHECKPOINT-
dc.subjectIONIZING-RADIATION-
dc.subjectPROTEIN COMPLEX-
dc.subjectSYNDROME CELLS-
dc.subjectMRE11 COMPLEX-
dc.subjectATM KINASE-
dc.subjectREPAIR-
dc.subjectPHOSPHORYLATION-
dc.subjectNBS1-
dc.titleDistinct functions of Nijmegen breakage syndrome in ataxia telangiectasia mutated-dependent responses to DNA damage-
dc.typeArticle-
dc.identifier.wosid000184283500005-
dc.identifier.scopusid2-s2.0-12444254801-
dc.type.rimsART-
dc.citation.volume1-
dc.citation.issue9-
dc.citation.beginningpage674-
dc.citation.endingpage681-
dc.citation.publicationnameMOLECULAR CANCER RESEARCH-
dc.embargo.liftdate9999-12-31-
dc.embargo.terms9999-12-31-
dc.contributor.localauthorLim, Dae-Sik-
dc.contributor.nonIdAuthorLee, Joo Hyeon-
dc.contributor.nonIdAuthorXu, Bo-
dc.contributor.nonIdAuthorLee, Chang-Hun-
dc.contributor.nonIdAuthorAhn, Jun-Young-
dc.contributor.nonIdAuthorSong, Min Sup-
dc.contributor.nonIdAuthorLee, Ho-
dc.contributor.nonIdAuthorCanman, Christine E.-
dc.contributor.nonIdAuthorLee, Jong-Soo-
dc.contributor.nonIdAuthorKastan, Michael B.-
dc.type.journalArticleArticle-
dc.subject.keywordPlusDOUBLE-STRAND BREAKS-
dc.subject.keywordPlusS-PHASE CHECKPOINT-
dc.subject.keywordPlusIONIZING-RADIATION-
dc.subject.keywordPlusPROTEIN COMPLEX-
dc.subject.keywordPlusSYNDROME CELLS-
dc.subject.keywordPlusMRE11 COMPLEX-
dc.subject.keywordPlusATM KINASE-
dc.subject.keywordPlusREPAIR-
dc.subject.keywordPlusPHOSPHORYLATION-
dc.subject.keywordPlusNBS1-
Appears in Collection
BS-Journal Papers(저널논문)
Files in This Item
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡ Click to see webofscience_button
⊙ Cited 52 items in WoS Click to see citing articles in records_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0