DNA double-strand break (DSB) repair by homologous recombination (HR) is thought to be restricted to the S- and G- phases of the cell cycle in part due to 53BP1 antagonizing DNA end resection in G-phase and non-cycling quiescent (G) cells. Here, we show that LIN37, a component of the DREAM transcriptional repressor, functions in a 53BP1-independent manner to prevent DNA end resection and HR in G cells. Loss of LIN37 leads to the expression of HR proteins, including BRCA1, BRCA2, PALB2, and RAD51, and promotes DNA end resection in G cells even in the presence of 53BP1. In contrast to 53BP1-deficiency, DNA end resection in LIN37-deficient G cells depends on BRCA1 and leads to RAD51 filament formation and HR. LIN37 is not required to protect DNA ends in cycling cells at G-phase. Thus, LIN37 regulates a novel 53BP1-independent cell phase-specific DNA end protection pathway that functions uniquely in quiescent cells.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416021 | PMC |
http://dx.doi.org/10.7554/eLife.68466 | DOI Listing |
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