The p400 ATPase Regulates Nucleosome Stability and Chromatin Ubiquitination During DNA Repair

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The p400 ATPase Regulates Nucleosome Stability and Chromatin Ubiquitination During DNA Repair

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dc.contributor.author Sun, Yingli
dc.contributor.author Xu, Ye
dc.contributor.author Jiang, Xiaofeng
dc.contributor.author Ayrapetov, Marina
dc.contributor.author Moskwa, Patryk Pawel
dc.contributor.author Yang, Shenghong
dc.contributor.author Weinstock, David Marc
dc.contributor.author Price, Brendan D.
dc.date.accessioned 2012-04-08T03:17:36Z
dc.date.issued 2010
dc.identifier.citation Xu, Ye, Yingli Sun, Xiaofeng Jiang, Marina K. Ayrapetov, Patryk Moskwa, Shenghong Yang, David M. Weinstock, and Brendan D. Price. 2010. The p400 ATPase regulates nucleosome stability and chromatin ubiquitination during DNA repair. The Journal of Cell Biology 191, no. 1: 31-43. en_US
dc.identifier.issn 0021-9525 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:8519633
dc.description.abstract The complexity of chromatin architecture presents a significant barrier to the ability of the DNA repair machinery to access and repair DNA double-strand breaks (DSBs). Consequently, remodeling of the chromatin landscape adjacent to DSBs is vital for efficient DNA repair. Here, we demonstrate that DNA damage destabilizes nucleosomes within chromatin regions that correspond to the \(\gamma\)-H2AX domains surrounding DSBs. This nucleosome destabilization is an active process requiring the ATPase activity of the p400 SWI/SNF ATPase and histone acetylation by the Tip60 acetyltransferase. p400 is recruited to DSBs by a mechanism that is independent of ATM but requires mdc1. Further, the destabilization of nucleosomes by p400 is required for the RNF8-dependent ubiquitination of chromatin, and for the subsequent recruitment of brca1 and 53BP1 to DSBs. These results identify p400 as a novel DNA damage response protein and demonstrate that p400-mediated alterations in nucleosome and chromatin structure promote both chromatin ubiquitination and the accumulation of brca1 and 53BP1 at sites of DNA damage. en_US
dc.language.iso en_US en_US
dc.publisher The Rockefeller University Press en_US
dc.relation.isversionof doi://10.1083/jcb.201001160 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2953432/pdf/ en_US
dash.license LAA
dc.title The p400 ATPase Regulates Nucleosome Stability and Chromatin Ubiquitination During DNA Repair en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal The Journal of Cell Biology en_US
dash.depositing.author Price, Brendan D.
dc.date.available 2012-04-08T03:17:36Z
dash.affiliation.other HMS^Radiation Oncology-BWH-DFCI-CH en_US

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