DNA-PK promotes DNA end resection at DNA double strand breaks in G<sub>0</sub> cells.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 35575473.
- Also identified by DOI 10.7554/eLife.74700 and PMC identifier 9122494.
- 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 is confined to the S and G<sub>2</sub> phases of the cell cycle partly due to 53BP1 antagonizing DNA end resection in G<sub>1</sub> phase and non-cycling quiescent (G<sub>0</sub>) cells where DSBs are predominately repaired by non-homologous end joining (NHEJ). Unexpectedly, we uncovered extensive MRE11- and CtIP-dependent DNA end resection at DSBs in G<sub>0</sub> murine and human cells. A whole genome CRISPR/Cas9 screen revealed the DNA-dependent kinase (DNA-PK) complex as a key factor in promoting DNA end resection in G<sub>0</sub> cells. In agreement, depletion of FBXL12, which promotes ubiquitylation and removal of the KU70/KU80 subunits of DNA-PK from DSBs, promotes even more extensive resection in G<sub>0</sub> cells. In contrast, a requirement for DNA-PK in promoting DNA end resection in proliferating cells at the G<sub>1</sub> or G<sub>2</sub> phase of the cell cycle was not observed. Our findings establish that DNA-PK uniquely promotes DNA end resection in G<sub>0</sub>, but not in G<sub>1</sub> or G<sub>2</sub> phase cells, which has important implications for DNA DSB repair in quiescent cells.
Medical subject headings
- DNA Breaks, Double-Stranded
- F-Box Proteins