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Molecular and Cellular Biology, March 2007, p. 1558-1567, Vol. 27, No. 5
0270-7306/07/$08.00+0     doi:10.1128/MCB.01495-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

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{triangledown}

Stephen E. Kearsey,1 Abigail L. Stevenson,1 Takashi Toda,2 and Shao-Win Wang1*

Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, United Kingdom,1 Cell Regulation Laboratory, London Research Institute, Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom2

Received 11 August 2006/ Returned for modification 19 September 2006/ Accepted 6 December 2006

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.


* Corresponding author. Mailing address: Department of Zoology, South Parks Road, Oxford OX1 3PS, United Kingdom. Phone: 44 1865 271212. Fax: 44 1865 271192. E-mail: shaowin.wang{at}zoo.ox.ac.uk.

{triangledown} Published ahead of print on 18 December 2006.


Molecular and Cellular Biology, March 2007, p. 1558-1567, Vol. 27, No. 5
0270-7306/07/$08.00+0     doi:10.1128/MCB.01495-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.