DNA End Resection: Mechanism and Control

Annu Rev Genet. 2021 Nov 23;55:285-307. doi: 10.1146/annurev-genet-071719-020312.

Abstract

DNA double-strand breaks (DSBs) are cytotoxic lesions that threaten genome integrity and cell viability. Typically, cells repair DSBs by either nonhomologous end joining (NHEJ) or homologous recombination (HR). The relative use of these two pathways depends on many factors, including cell cycle stage and the nature of the DNA ends. A critical determinant of repair pathway selection is the initiation of 5'→3' nucleolytic degradation of DNA ends, a process referred to as DNA end resection. End resection is essential to create single-stranded DNA overhangs, which serve as the substrate for the Rad51 recombinase to initiate HR and are refractory to NHEJ repair. Here, we review recent insights into the mechanisms of end resection, how it is regulated, and the pathological consequences of its dysregulation.

Keywords: 53BP1; CtIP; DNA repair; DNA2; EXO1; MRE11-RAD50-NBS1; homologous recombination.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • DNA
  • DNA Breaks, Double-Stranded*
  • DNA End-Joining Repair / genetics
  • DNA Repair / genetics
  • DNA-Binding Proteins* / metabolism
  • Exodeoxyribonucleases / genetics
  • Exodeoxyribonucleases / metabolism
  • Homologous Recombination / genetics

Substances

  • DNA-Binding Proteins
  • DNA
  • Exodeoxyribonucleases