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

The RecQ family of DNA helicases have been shown to be important for the ma intenance 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 c ondition, Werner's syndrome. Several pieces of evidence suggest that RecQ f amily helicases form associations with one or more of the cellular topoisom erases, and together these heteromeric complexes manipulate DNA structure t o effect efficient DNA replication, genetic recombination, or both. Here, w e propose that RecQ helicases are required for ensuring that structural abn ormalities arising during replication, such as at sites where replication f orks encounter DNA lesions, are corrected with high fidelity. In mutants de fective in these proteins, not only is replication abnormal, but cells disp lay aberrant responses to DNA-damaging agents or inhibitors of DNA synthesi s. We suggest that RecQ helicases may be important for the integration of c ellular responses to these insults, such as by linking cell cycle checkpoin t responses to recombinational repair. BioEssays 21:286-294, 1999. (C) 1999 John Wiley & Sons, Inc.