Double-strand break end resection and repair pathway choice

Annu Rev Genet. 2011;45:247-71. doi: 10.1146/annurev-genet-110410-132435. Epub 2011 Sep 12.

Abstract

DNA double-strand breaks (DSBs) are cytotoxic lesions that can result in mutagenic events or cell death if left unrepaired or repaired inappropriately. Cells use two major pathways for DSB repair: nonhomologous end joining (NHEJ) and homologous recombination (HR). The choice between these pathways depends on the phase of the cell cycle and the nature of the DSB ends. A critical determinant of repair pathway choice is the initiation of 5'-3' resection of DNA ends, which commits cells to homology-dependent repair, and prevents repair by classical NHEJ. Here, we review the components of the end resection machinery, the role of end structure, and the cell-cycle phase on resection and the interplay of end processing with NHEJ.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cell Cycle
  • DNA Breaks, Double-Stranded*
  • DNA End-Joining Repair*
  • DNA Helicases / chemistry
  • DNA Helicases / genetics
  • Exodeoxyribonucleases / chemistry
  • Exodeoxyribonucleases / genetics
  • Fanconi Anemia / genetics
  • Gene Expression Regulation, Fungal
  • Genes, BRCA1
  • Genes, Fungal*
  • Genes, cdc
  • Humans
  • Protein Conformation
  • Recombinational DNA Repair
  • Saccharomyces cerevisiae / chemistry
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Translocation, Genetic

Substances

  • Saccharomyces cerevisiae Proteins
  • Exodeoxyribonucleases
  • exodeoxyribonuclease I
  • DNA Helicases
  • DNA2 protein, S cerevisiae