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. 2007 Jun;9(6):683-90.
doi: 10.1038/ncb1599. Epub 2007 May 7.

Roles of ATM and NBS1 in chromatin structure modulation and DNA double-strand break repair

Elijahu Berkovich  1 , Raymond J Monnat Jr, Michael B Kastan
Affiliations

Roles of ATM and NBS1 in chromatin structure modulation and DNA double-strand break repair

Elijahu Berkovich et al. Nat Cell Biol. 2007 Jun.

Abstract

We developed a novel system to create DNA double-strand breaks (DSBs) at defined endogenous sites in the human genome, and used this system to detect protein recruitment and loss at and around these breaks by chromatin immunoprecipitation (ChIP). The detection of human ATM protein at site-specific DSBs required functional NBS1 protein, ATM kinase activity and ATM autophosphorylation on Ser 1981. DSB formation led to the localized disruption of nucleosomes, a process that depended on both functional NBS1 and ATM. These two proteins were also required for efficient recruitment of the repair cofactor XRCC4 to DSBs, and for efficient DSB repair. These results demonstrate the functional importance of ATM kinase activity and phosphorylation in the response to DSBs, and support a model in which ordered chromatin structure changes that occur after DNA breakage depend on functional NBS1 and ATM, and facilitate DNA DSB repair.

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