A role for the fission yeast Rqh1 helicase in chromosome segregation.
Schizosaccharomyces pombe Rqh1 protein is a member of the RecQ DNA helicase family. Members of this protein family are mutated in several human genome instability syndromes, including Bloom, Werner and Rothmund-Thomson syndromes. RecQ helicases participate in recombination repair of stalled replication forks or DNA breaks, but the precise mechanisms that lead to the development of cancer in these diseases have remained obscure. Here, we reveal a function for Rqh1 in chromosome segregation even in the absence of exogenous insult to the DNA. We show that cells lacking Rqh1 are delayed in anaphase progression, and show lagging chromosomal DNA, which is particularly apparent in the rDNA locus. This mitotic delay is dependent on the spindle checkpoint, as deletion of mad2 abolishes the delay as well as the accumulation of Cut2 in rqh1delta cells. Furthermore, relieving replication fork arrest in the rDNA repeat by deletion of reb1+ partially suppresses rqh1delta phenotypes. These data are consistent with the function of the Top3-RecQ complex in maintenance of the rDNA structure by processing aberrant chromosome structures arising from DNA replication. The chromosome segregation defects seen in the absence of functional RecQ helicases may contribute to the pathogenesis of human RecQ helicase disorders.
Win
Thein Z
TZ
Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS, UK.
Mankouri
Hocine W
HW
Hickson
Ian D
ID
Wang
Shao-Win
SW
D000015:Abnormalities, Multiple / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000705:Anaphase / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism; D020090:Chromosome Segregation / Q000502:physiology*; D004265:DNA Helicases / Q000172:deficiency / Q000378:metabolism*; D006801:Humans; D064246:Mad2 Proteins; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000172:deficiency / Q000378:metabolism; D012568:Schizosaccharomyces / Q000201:enzymology* / Q000235:genetics; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*; D013577:Syndrome
D018797:Cell Cycle Proteins; D064246:Mad2 Proteins; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D029702:Schizosaccharomyces pombe Proteins; C577696:mad2 protein, S pombe; D004265:DNA Helicases; C106462:Rqh1 protein, S pombe