LIN37-DREAM prevents DNA end resection and homologous recombination at DNA double-strand breaks in quiescent cells
Bo-Ruei Chen, Yinan Wang, Anthony Tubbs, Dali Zong, Faith Fowler, Nicholas Zolnerowich, Wei Wu, Amelia Bennett, Chun-Chin Chen, Wendy Feng, André Nussenzweig, Jessica K. Tyler, Barry P. Sleckman
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 the expression of HR proteins, including BRCA1, BRCA2, PALB2, and RAD51, and promotes 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.