|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|
|Date Published||2021 09 03|
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.
|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
Jessica K. Tyler, Ph.D.