Involvement of Homologous Recombination in Carcinogenesis

Adv Genet. 2007;58:67-87. doi: 10.1016/S0065-2660(06)58003-4.

Abstract

DNA alterations of every type are associated with the incidence of carcinogenesis, often on the genomic scale. Although homologous recombination (HR) is an important pathway of DNA repair, evidence is accumulating that deleterious genomic rearrangements can result from HR. It therefore follows that HR events may play a causative role in carcinogenesis. HR is elevated in response to carcinogens. HR may also be increased or decreased when its upstream regulation is perturbed or components of the HR machinery itself are not fully functional. This chapter summarizes research findings that demonstrate an association between HR and carcinogenesis. Increased or decreased frequencies of HR have been found in cancer cells and cancer-prone hereditary human disorders characterized by mutations in genes playing a role in HR, such as ATM, Tp53, BRCA, BLM, and WRN genes. Another evidence linking perturbations in HR and carcinogenesis is provided by studies showing that exposure to carcinogens results in an increased frequency of HR resulting in DNA deletions in yeast, human cells, or mice.

Publication types

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

MeSH terms

  • Adenosine Triphosphatases / physiology
  • Animals
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins / physiology
  • DNA Helicases / physiology
  • DNA Repair / physiology
  • DNA-Binding Proteins / physiology
  • Exodeoxyribonucleases
  • Fanconi Anemia Complementation Group Proteins / physiology
  • Genes, BRCA1 / physiology
  • Genes, BRCA2 / physiology
  • Genes, p53 / physiology
  • Humans
  • Models, Biological
  • Models, Theoretical
  • Neoplasms / genetics*
  • Protein-Serine-Threonine Kinases / physiology
  • Rad51 Recombinase / physiology
  • RecQ Helicases / physiology
  • Recombination, Genetic / physiology*
  • Tumor Suppressor Proteins / physiology
  • Werner Syndrome Helicase

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Fanconi Anemia Complementation Group Proteins
  • Tumor Suppressor Proteins
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Atm protein, mouse
  • Protein-Serine-Threonine Kinases
  • Rad51 Recombinase
  • Exodeoxyribonucleases
  • Adenosine Triphosphatases
  • Bloom syndrome protein
  • DNA Helicases
  • RecQ Helicases
  • WRN protein, human
  • Werner Syndrome Helicase