Division of Hematology and Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, United States; O’Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, United States
Yinan Wang
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, United States
Anthony Tubbs
Laboratory of Genome Integrity, National Cancer Institute, Bethesda, United States
Dali Zong
Laboratory of Genome Integrity, National Cancer Institute, Bethesda, United States
Faith C Fowler
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, United States
Nicholas Zolnerowich
Laboratory of Genome Integrity, National Cancer Institute, Bethesda, United States
Wei Wu
Laboratory of Genome Integrity, National Cancer Institute, Bethesda, United States
Amelia Bennett
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, United States
Chun-Chin Chen
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, United States
Division of Hematology and Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, United States; O’Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, United States
DNA double-strand break (DSB) repair by homologous recombination (HR) is thought to be restricted to the S- and G2- phases of the cell cycle in part due to 53BP1 antagonizing DNA end resection in G1-phase and non-cycling quiescent (G0) 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 G0 cells. Loss of LIN37 leads to the expression of HR proteins, including BRCA1, BRCA2, PALB2, and RAD51, and promotes DNA end resection in G0 cells even in the presence of 53BP1. In contrast to 53BP1-deficiency, DNA end resection in LIN37-deficient G0 cells depends on BRCA1 and leads to RAD51 filament formation and HR. LIN37 is not required to protect DNA ends in cycling cells at G1-phase. Thus, LIN37 regulates a novel 53BP1-independent cell phase-specific DNA end protection pathway that functions uniquely in quiescent cells.
