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bioRxiv · 10.1101/2024.03.28.587286

SMARCA2 and SMARCA4 participate in DNA damage repair

Wu, D.·Yu, L.
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Abstract

SMARCA2 and SMARCA4 (SMARCA2/4) are paralogs and act as the key enzymatic subunits in the SWI/SNF complex for chromatin remodeling. However, the role of SMARCA2/4 in DNA damage response remains unclear. Here, we show that SMARCA2/4 relocate to DNA lesions in response to DNA damage, which requires their ATPase activities. Moreover, these ATPase activities are also required for the relocation of other subunits in the SWI/SNF complex to DNA lesions. Interestingly, the relocation of SMARCA2/4 is independent of {gamma}H2AX, ATM, ATR, p300/CBP, or PARP1/2, indicating that it may directly recognize DNA lesions as a DNA damage sensor. Lacking SMARCA2/4 prolongs the retention of {gamma}H2AX, RNF8 and BRCA1 at DNA lesions and impairs RAD51-dependent homologous recombination repair. Moreover, the treatment of SMARCA2/4 inhibitor sensitizes tumor cells to PARP inhibitor treatment. Collectively, this study reveals SMARCA2/4 as a DNA damage repair factor for double-strand break repair.

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Wu, D., Yu, L.. 2024-03-29. SMARCA2 and SMARCA4 participate in DNA damage repair. https://doi.org/10.1101/2024.03.28.587286

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