Original Research ARTICLE
The chromatin remodeling protein BRG1 modulates BRCA1 response to UV irradiation by regulating ATR/ATM activation
- 1Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL, USA
- 2Perinatal Research Laboratories, Department of Obstetrics and Gynecology, David-Geffen School of Medicine at University of California Los Angeles, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles Medical Center, Torrance, CA, USA
The SWI/SNF chromatin remodeling complex plays a role in the repair of UV-induced DNA damage. It was proposed that chromatin remodeling activities are utilized to increase the accessibility of nucleotide excision repair (NER) machinery and checkpoint factors to the damaged DNA. It was shown recently that BRCA1 contributes to UV damage response by promoting photoproduct excision, triggering post-UV checkpoint activation and post-replicative repair. In this study, we show that BRCA1 rapidly binds to UV damage sites when cells are undergoing DNA synthesis. In contrast, two phosphorylated forms of BRCA1 do not accumulate at sites of UV damage. Depletion of BRG1, a core subunit of the human SWI/SNF-BAF complex, impairs the recruitment of BRCA1 to the damage sites and attenuates DNA damage induced BRCA1 phosphorylation. At UV lesions-stalled replication forks, BRG1 promotes RPA phosphorylation in response to UV irradiation, since UV-induced phosphorylation of chromatin bound RPA drops significantly when BRG1 is depleted in human cells. Importantly, activation of the ATM/ATR kinases is attenuated when BRG1 is depleted. We propose that BRG1 modulates BRCA1 response to UV irradiation by regulating ATM/ATR activation.
Keywords: BRG1, SWI/SNF, BRCA1, ATR/ATM, nucleotide excision repair, UV irradiation, DNA damage response, RPA
Citation: Zhang L, Chen H, Gong M and Gong F (2013) The chromatin remodeling protein BRG1 modulates BRCA1 response to UV irradiation by regulating ATR/ATM activation. Front. Oncol. 3:7. doi: 10.3389/fonc.2013.00007
Received: 03 October 2012; Accepted: 09 January 2013;
Published online: 23 January 2013.
Edited by:Mira Jung, Georgetown University, USA
Copyright: © 2013 Zhang, Chen, Gong and Gong. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
*Correspondence: Feng Gong, Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, 1150 Northwest 14th Street, Miami, FL 33156, USA. e-mail: email@example.com