4.6 Article

The chromatin remodeling factor BRG1 stimulates nucleotide excision repair by facilitating recruitment of XPC to sites of DNA damage

Journal

CELL CYCLE
Volume 8, Issue 23, Pages 3953-3959

Publisher

LANDES BIOSCIENCE
DOI: 10.4161/cc.8.23.10115

Keywords

BRG1; SWI/SNF; nucleotide excision repair; UV radiation; DNA damage

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Funding

  1. Concern Foundation for Cancer Research
  2. American Cancer Society
  3. Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine
  4. NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [R01ES017784] Funding Source: NIH RePORTER

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BRG1 is a catalytic subunit of the human SWI/SNF-like BAF chromatin remodeling complexes. Recent findings have shown that inactivation of BRG1 sensitizes mammalian cells to various DNA damaging agents, including ultraviolet (UV) and ionizing radiation. However, it is unclear whether BRG1 facilitates nucleotide excision repair (NER). Here we show that re-expression of BRG1 in cells lacking endogenous BRG1 expression stimulates nucleotide excision repair of UV induced DNA damage. Using a micropore UV radiation technique, we demonstrate that recruitment of the DNA damage recognition protein XPC to sites of UV lesions is disrupted when BRG1 is stably depleted. Chromatin immunoprecipitation of the endogenous DDB2 protein, which is involved in recruiting XPC to UV-induced CPDs (cyclobutane pyrimidine dimers), shows that elevated levels of BRG1 are associated with DDB2 in chromatin in response to UV radiation. Additionally, we detected slow BRG1 accumulation at sites of UV lesions. Our findings suggest that the chromatin remodeling factor BRG1 is recruited to sites of UV lesions to facilitate NER in human chromatin.

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