DNA helicase deficiencies associated with cancer predisposition and premature ageing disorders

Deficiency in a helicase of the RecQ family is found in at least three huma n genetic disorders associated with cancer predisposition and/or premature ageing. The RecQ helicases encoded by the BLM, WRN and RECQ4 genes are defe ctive in Bloom's, Werner's and Rothmund-Thomson syndromes, respectively. Ce lls derived from individuals with these disorders in each case show inheren t genomic instability, Recent studies have demonstrated direct interactions between these RecQ helicases and human nuclear proteins required for sever al aspects of chromosome maintenance, including p53, BRCA1, topoisomerase I II, replication protein A and DNA polymerase delta. Here, we review this ne twork of protein interactions, and the clues that they present regarding th e potential roles of RecQ family members in DNA repair, replication and/or recombination pathways.