AI Article Synopsis
- Mammalian SWI/SNF chromatin remodeling complexes are known for their role in transcription but have been found to also be crucial in repairing DNA double-strand breaks (DSBs).
- Inactivation of these complexes leads to inefficient DSB repair, increased sensitivity to DNA damage, and defects in gamma-H2AX phosphorylation, which is important for DSB repair signaling.
- The SWI/SNF complexes interact with gamma-H2AX in damaged chromatin, suggesting they assist in the repair process by promoting phosphorylation of H2AX, although they do not alter the expression of key DSB repair genes or DNA damage checkpoints.
Article Abstract
Although mammalian SWI/SNF chromatin remodeling complexes have been well established to play important role in transcription, their role in DNA repair has remained largely unexplored. Here we show that inactivation of the SWI/SNF complexes and downregulation of the catalytic core subunits of the complexes both result in inefficient DNA double-strand break (DSB) repair and increased DNA damage sensitivity as well as a large defect in H2AX phosphorylation (gamma-H2AX) and nuclear focus formation after DNA damage. The expression of most DSB repair genes remains unaffected and DNA damage checkpoints are grossly intact in the cells inactivated for the SWI/SNF complexes. Although the SWI/SNF complexes do not affect the expression of ATM, DNA-PK and ATR, or their activation and/or recruitment to DSBs, they rapidly bind to DSB-surrounding chromatin via interaction with gamma-H2AX in the manner that is dependent on the amount of DNA damage. Given the crucial role for gamma-H2AX in efficient DSB repair, these results suggest that the SWI/SNF complexes facilitate DSB repair, at least in part, by promoting H2AX phosphorylation by directly acting on chromatin.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1560357 | PMC |
| http://dx.doi.org/10.1038/sj.emboj.7601291 | DOI Listing |
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