Five members of the RecQ subfamily of DEx-H-containing
DNA helicases have been identified in both human and mouse, and mutations in BLM, WRN, and RECQ4 are associated with human diseases of
premature aging,
cancer, and
chromosomal instability. Although a
genetic disease has not been linked to RECQ1 mutations, RECQ1 helicase is the most highly expressed of the human
RecQ helicases, suggesting an important role in cellular
DNA metabolism. Recent advances have elucidated a unique role of RECQ1 to suppress
genomic instability. Embryonic fibroblasts from RECQ1-deficient mice displayed
aneuploidy,
chromosomal instability, and increased load of DNA damage.(1) Acute depletion of human RECQ1 renders cells sensitive to DNA damage and results in spontaneous gamma-H2AX foci and elevated sister chromatid exchanges, indicating aberrant repair of DNA breaks.(2) Consistent with a role in DNA repair, RECQ1 relocalizes to irradiation-induced nuclear foci and associates with
chromatin.(2) RECQ1 catalytic activities(3) and interactions with DNA repair
proteins(2,4,5) are likely to be important for its molecular functions in genome homeostasis. Collectively, these studies provide the first evidence for an important role of RECQ1 to confer
chromosomal stability that is unique from that of other
RecQ helicases and suggest its potential involvement in
tumorigenesis.