LIN37-DREAM prevents DNA end resection and homologous recombination at DNA double-strand breaks in quiescent cells.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34477552.
- Also identified by DOI 10.7554/eLife.68466 and PMC identifier 8416021.
- Licence recorded as CC0.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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 proteins, including BRCA1, BRCA2, PALB2, and RAD51, and promotes DNA end resection in G<sub>0</sub> cells even in the presence of 53BP1. In contrast to 53BP1-deficiency, DNA end resection in LIN37-deficient G<sub>0</sub> 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<sub>1</sub>-phase. Thus, LIN37 regulates a novel 53BP1-independent cell phase-specific DNA end protection pathway that functions uniquely in quiescent cells.
Medical subject headings
- DNA Breaks, Double-Stranded
- DNA End-Joining Repair
- Rad51 Recombinase
- Trans-Activators