Title | LIN37-DREAM prevents DNA end resection and homologous recombination at DNA double-strand breaks in quiescent cells. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Chen B-R, Wang Y, Tubbs A, Zong D, Fowler FC, Zolnerowich N, Wu W, Bennett A, Chen C-C, Feng W, Nussenzweig A, Tyler JK, Sleckman BP |
Journal | Elife |
Volume | 10 |
Date Published | 2021 09 03 |
ISSN | 2050-084X |
Abstract | 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. |
DOI | 10.7554/eLife.68466 |
Alternate Journal | Elife |
PubMed ID | 34477552 |
PubMed Central ID | PMC8416021 |
Grant List | P30 CA013148 / CA / NCI NIH HHS / United States R01 CA095641 / CA / NCI NIH HHS / United States R01 AI074953 / AI / NIAID NIH HHS / United States R01 GM064475 / GM / NIGMS NIH HHS / United States R01 AI047829 / AI / NIAID NIH HHS / United States |
Related Faculty:
Jessica K. Tyler, Ph.D.