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LIN37-DREAM prevents DNA end resection and homologous recombination at DNA double-strand breaks in quiescent cells.

ABSTRACT: 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.

SUBMITTER: Chen BR 

PROVIDER: S-EPMC8416021 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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LIN37-DREAM prevents DNA end resection and homologous recombination at DNA double-strand breaks in quiescent cells.

Chen Bo-Ruei BR   Wang Yinan Y   Tubbs Anthony A   Zong Dali D   Fowler Faith C FC   Zolnerowich Nicholas N   Wu Wei W   Bennett Amelia A   Chen Chun-Chin CC   Feng Wendy W   Nussenzweig Andre A   Tyler Jessica K JK   Sleckman Barry P BP  

eLife 20210903

DNA double-strand break (DSB) repair by homologous recombination (HR) is thought to be restricted to the S- and G<sub>2</sub>- phases of the cell cycle in part due to 53BP1 antagonizing DNA end resection in G<sub>1</sub>-phase and non-cycling quiescent (G<sub>0</sub>) 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<sub>0</sub> cells. Loss of LIN37 leads to the expression of HR pr  ...[more]

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