Defending genome integrity during DNA replication: a proposed role for RecQ family helicases

Bioessays. 1999 Apr;21(4):286-94. doi: 10.1002/(SICI)1521-1878(199904)21:4<286::AID-BIES4>3.0.CO;2-Z.

Abstract

The RecQ family of DNA helicases have been shown to be important for the maintenance of genomic integrity in all organisms analysed to date. In human cells, representatives of this family include the proteins defective in the cancer predisposition disorder Bloom's syndrome and the premature ageing condition, Werner's syndrome. Several pieces of evidence suggest that RecQ family helicases form associations with one or more of the cellular topoisomerases, and together these heteromeric complexes manipulate DNA structure to effect efficient DNA replication, genetic recombination, or both. Here, we propose that RecQ helicases are required for ensuring that structural abnormalities arising during replication, such as at sites where replication forks encounter DNA lesions, are corrected with high fidelity. In mutants defective in these proteins, not only is replication abnormal, but cells display aberrant responses to DNA-damaging agents or inhibitors of DNA synthesis. We suggest that RecQ helicases may be important for the integration of cellular responses to these insults, such as by linking cell cycle checkpoint responses to recombinational repair.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine Triphosphatases / metabolism*
  • Animals
  • Bloom Syndrome / genetics
  • Bloom Syndrome / metabolism
  • DNA Helicases / metabolism*
  • DNA Repair
  • DNA Replication / genetics*
  • DNA Replication / physiology*
  • DNA Topoisomerases, Type I / metabolism
  • Genome
  • Humans
  • Longevity / genetics
  • Models, Biological
  • RecQ Helicases
  • Werner Syndrome / genetics
  • Werner Syndrome / metabolism

Substances

  • Adenosine Triphosphatases
  • RECQL protein, human
  • DNA Helicases
  • RecQ Helicases
  • DNA Topoisomerases, Type I