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.

Journal article

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: Kearsey, S; Stevenson, A; Toda, T; Wang, S

• Publication status: Published
• Journal: Molecular and cellular biology
• Volume: 27
• Issue: 5
• Pages: 1558-1567
• Publication date: 2007-03-01
• DOI: 10.1128/mcb.01495-06
• EISSN: 1098-5549
• ISSN: 0270-7306
• Language: English
• Keywords: Fungal Proteins; Schizosaccharomyces pombe Proteins; DNA Breaks, Double-Stranded; DNA Repair; Immunohistochemistry; Schizosaccharomyces; DNA, Ribosomal; Cell Cycle Proteins; DNA, Fungal; DNA Helicases