DNA-PK promotes DNA end resection at DNA double strand breaks in G0 cells. Academic Article uri icon

Overview

abstract

  • DNA double-strand break (DSB) repair by homologous recombination is confined to the S and G2 phases of the cell cycle partly due to 53BP1 antagonizing DNA end resection in G1 phase and non-cycling quiescent (G0) 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 G0 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 G0 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 G0 cells. In contrast, a requirement for DNA-PK in promoting DNA end resection in proliferating cells at the G1 or G2 phase of the cell cycle was not observed. Our findings establish that DNA-PK uniquely promotes DNA end resection in G0, but not in G1 or G2 phase cells, which has important implications for DNA DSB repair in quiescent cells.

publication date

  • May 16, 2022

Research

keywords

  • DNA Breaks, Double-Stranded
  • F-Box Proteins

Identity

PubMed Central ID

  • PMC9122494

Scopus Document Identifier

  • 85130767435

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2008.08.037

PubMed ID

  • 35575473

Additional Document Info

volume

  • 11