Abstract 1965: Cross-talk among the components of DNA damage response and chromatin remodeling

Abstract

Abstract Chromatin remodeling is integral to the functionality of many DNA-templated processes, including DNA damage repair and damage induced checkpoint signaling. The coordinated response to genotoxic damage begins by recruitment of specific protein factors exhibiting a high degree of cross-talk to orchestrate individual pathway events. The common initial step, i.e., accessing DNA damage embedded within chromatin, is a key factor in determining the course of DNA damage response and efficiency of damage processing. Our recent studies have sought to understand the roles for the mammalian SWI-SNF components in nucleotide excision repair (NER) and checkpoint activation. We have knocked down Brg1, the catalytic component and SNF5, the core component, of the SWI-SNF complex, and assessed the impact of these knockdowns on NER and checkpoint activation. Our data suggest that SWI-SNF complex associates with UV damaged chromatin through its interaction with damage recognition factor XPC and helps stabilization of XPC at the damage site. Furthermore, SWI-SNF influences the access of ATM at the damage site, which promotes assembly of ATM-γH2AX-MDC1-53BP1-BRCA1 complex, and eventually influences NER. We propose that SWI-SNF complex positively modulates NER by facilitating stability and accessibility of NER and checkpoint factors at the UV damaged chromatin sites. (This work was supported by NIH grants CA93413, ES2388 and ES12991) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1965.