title: Fission yeast Cut8 is required for the repair of DNA double-strand breaks, ribosomal DNA maintenance, and cell survival in the absence of Rqh1 helicase.
abstract: Schizosaccharomyces pombe Rqh1 is a member of the RecQ DNA helicase family. Members of this protein family are mutated in cancer predisposition diseases, causing Bloom's, Werner, and Rothmund-Thomson syndromes. Rqh1 forms a complex with topoisomerase III and is proposed to process or disrupt aberrant recombination structures that arise during S phase to allow proper chromosome segregation during mitosis. Intriguingly, in the absence of Rqh1, processing of these structures appears to be dependent on Rad3 (human ATR) in a manner that is distinct from its role in checkpoint control. Here, we show that rad3 rqh1 mutants are normally committed to a lethal pathway of DNA repair requiring homologous recombination, but blocking this pathway by Rhp51 inactivation restores viability. Remarkably, viability is also restored by overexpression of Cut8, a nuclear envelope protein involved in tethering and proper function of the proteasome. In keeping with a recently described function of the proteasome in the repair of DNA double-strand breaks, we found that Cut8 is also required for DNA double-strand break repair and is essential for proper chromosome segregation in the absence of Rqh1, suggesting that these proteins might function in a common pathway in homologous recombination repair to ensure accurate nuclear division in S. pombe.
authors.affiliation: Department of Zoology, South Parks Road, Oxford OX1 3PS, United Kingdom. shaowin.wang@zoo.ox.ac.uk
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Kearsey
authors.forename: Abigail L
authors.initials: AL
authors.lastname: Stevenson
authors.forename: Takashi
authors.initials: T
authors.lastname: Toda
authors.forename: Shao-Win
authors.initials: SW
authors.lastname: Wang
mesh_terms: D018797:Cell Cycle Proteins / Q000502:physiology*; D053903:DNA Breaks, Double-Stranded; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D004271:DNA, Fungal; D004275:DNA, Ribosomal / Q000378:metabolism*; D005656:Fungal Proteins / Q000502:physiology*; D007150:Immunohistochemistry; D012568:Schizosaccharomyces / Q000201:enzymology / Q000235:genetics*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; C088892:Cut8 protein, S pombe; D004271:DNA, Fungal; D004275:DNA, Ribosomal; D005656:Fungal Proteins; D029702:Schizosaccharomyces pombe Proteins; D004265:DNA Helicases; C106462:Rqh1 protein, S pombe