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Molecular and Cellular Biology, November 2007, p. 7439-7450, Vol. 27, No. 21
0270-7306/07/$08.00+0     doi:10.1128/MCB.00963-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The Human F-Box DNA Helicase FBH1 Faces Saccharomyces cerevisiae Srs2 and Postreplication Repair Pathway Roles

Irene Chiolo,^1,2, Marco Saponaro,^1,2 Anastasia Baryshnikova,^1,2, Jeong-Hoon Kim,³ Yeon-Soo Seo,³ and Giordano Liberi^1,2*

FIRC Institute of Molecular Oncology Foundation, Via Adamello 16, 20139 Milan, Italy,¹ Dipartimento di Scienze Biomolecolari e Biotecnologie, Università degli Studi di Milano, Via Celoria 26, 20133 Milan, Italy,² Department of Biological Sciences, National Creative Research Initiative Center for Cell Cycle Control, Korea Advanced Institute of Science and Technology, Daejeon 305-701, South Korea³

Received 31 May 2007/ Returned for modification 28 June 2007/ Accepted 14 August 2007

The Saccharomyces cerevisiae Srs2 UvrD DNA helicase controls genome integrity by preventing unscheduled recombination events. While Srs2 orthologues have been identified in prokaryotic and lower eukaryotic organisms, human orthologues of Srs2 have not been described so far. We found that the human F-box DNA helicase hFBH1 suppresses specific recombination defects of S. cerevisiae srs2 mutants, consistent with the finding that the helicase domain of hFBH1 is highly conserved with that of Srs2. Surprisingly, hFBH1 in the absence of SRS2 also suppresses the DNA damage sensitivity caused by inactivation of postreplication repair-dependent functions leading to PCNA ubiquitylation. The F-box domain of hFBH1, which is not present in Srs2, is crucial for hFBH1 functions in substituting for Srs2 and postreplication repair factors. Furthermore, our findings indicate that an intact F-box domain, acting as an SCF ubiquitin ligase, is required for the DNA damage-induced degradation of hFBH1 itself. Overall, our findings suggest that the hFBH1 helicase is a functional human orthologue of budding yeast Srs2 that also possesses self-regulation properties necessary to execute its recombination functions.

Published ahead of print on 27 August 2007.

Present address: Department of Genome and Computational Biology, Lawrence Berkeley National Laboratory, MS 84-171, 1 Cyclotron Road, Berkeley, CA 94720.

Present address: Banting and Best Department of Medical Research and Department of Medical Genetics and Microbiology, University of Toronto, Toronto, Canada.

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