LIN37-DREAM Prevents DNA End Resection and Homologous Recombination at DNA Double Strand Breaks in Quiescent Cells

Academic Article

Abstract

  • DNA double strand break (DSB) repair by homologous recombination (HR) is thought to be restricted to the S- and G 2 - phases of the cell cycle in part due to 53BP1 antagonizing DNA end resection in G 1 -phase and non-cycling quiescent (G 0 ) 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 0 cells. Loss of LIN37 leads to expression of HR proteins, including BRCA1, BRCA2, PALB2 and RAD51, and DNA end resection in G 0 cells even in the presence of 53BP1. In contrast to 53BP1-deficiency, DNA end resection in LIN37-deficient G 0 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 1 -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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    Author List

  • Chen B-R; Wang Y; Tubbs A; Zong D; Fowler F; Zolnerowich N; Wu W; Bennett A; Chen C-C; Feng W