Helicase activity is only partially required for Schizosaccharomyces pombe Rqh1p function

Abstract

The RecQ-related family of DNA helicases is required for the maintenance of genomic stability in organisms ranging from bacteria to humans. In humans, mutation of three RecQ-related helicases, BLM, WRN and RecQL4, cause the cancer-prone and premature ageing diseases of Bloom syndrome, Werner's syndrome and Rothmund-Thompson syndrome, respectively. In the fission yeast Schizosaccharomyces pombe, disruption of the rqh1(+) gene, which encodes the single Sz. pombe RecQ-related helicase, causes cells to display reduced viability and elevated levels of chromosome loss. After S-phase arrest or DNA damage, cells lacking rqh1(+) function display elevated levels of homologous recombination and defective chromosome segregation. Here we show that, like other RecQ family members, the Rqh1p protein displays 3' to 5' DNA helicase activity. Interestingly, however, unlike other RecQ family members, the helicase activity of Rqh1p is only partially required for its function in recovery from S-phase arrest or DNA damage. We also report that high cellular levels of Rqh1p result in lethal chromosome segregation defects, while more moderate levels of Rqh1p cause significantly elevated rates of chromosome loss. This suggests that careful regulation of RecQ-like protein levels in eukaryotic cells is vital for maintaining genome stability.