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| Subject Categories: Cell Cycle | Genome Stability & Dynamics |
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| The EMBO Journal
(2005) 24, 405–417, doi:10.1038/sj.emboj.7600511 Published online 23 December 2004 |
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| Mechanistically distinct roles for Sgs1p in checkpoint activation and replication fork maintenance |
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| Lotte Bjergbaek, Jennifer A Cobb, Monica Tsai-Pflugfelder and Susan M Gasser |
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Department of Molecular Biology and NCCR, Frontiers in Genetics, University of Geneva, Quai Ernest-Ansermet 30, Geneva, Switzerland To whom correspondence should be addressed Susan M Gasser, Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland. Tel.: +41 61 697 7255; Fax: +41 61 697 3976; E-mail: susan.gasser@fmi.ch Received 3 August 2004; Accepted 19 November 2004; Published online 23 December 2004. |
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| Abstract |
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The RecQ helicase Sgs1p forms a complex with the type 1 DNA topoisomerase Top3p that resolves double Holliday junctions resulting from Rad51-mediated exchange. We find, however, that Sgs1p functions independently of both Top3p and Rad51p to stimulate the checkpoint kinase Rad53p when replication forks stall due to dNTP depletion on hydroxyurea. Checkpoint activation does not require Sgs1p function as a helicase, and correlates with its ability to bind the Rad53p kinase FHA1 motif directly. On the other hand, Sgs1p's helicase activity is required together with Top3p and the strand-exchange factor Rad51p, to help stabilise DNA polymerase  at stalled replication forks. In this function, the Sgs1p/Top3p complex acts in parallel to the Claspin-related adaptor, Mrc1p, although the sgs1 and mrc1 mutations are epistatic for Rad53p activation. We thus identify two distinct pathways through which Sgs1p contributes to genomic integrity: checkpoint kinase activation requires Sgs1p as a noncatalytic Rad53p-binding site, while the combined Top3p/Sgs1p resolvase activity contributes to replisome stability and recovery from arrested replication forks. |
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| Keywords: DNA polymerase stabilisation, Rad53 activation, Sgs1p, S-phase checkpoint, Top3 |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSNature Structural Biology News and Views (01 Oct 2003) Nature Genetics News and Views (01 Jun 2007) RESEARCHDNA polymerase stabilization at stalled replication forks requires Mec1 and the RecQ helicase Sgs1 The EMBO Journal Article (15 Aug 2003) DNA polymerase stabilization at stalled replication forks requires Mec1 and the RecQ helicase Sgs1 The EMBO Journal Article (15 Aug 2003) |
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