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RESEARCH PAPER
1 F.I.R.C. Institute of Molecular Oncology Foundation, 20141, Milan, Italy and Dipartimento di Scienze Biomolecolari e Biotecnologie, University of Milan, Milan, Italy; 2 Rosenstiel Center and Department of Biology, Brandeis University, Waltham, Massachusetts, USA
S-phase cells overcome chromosome lesions through replication-coupled recombination processes that seem to be assisted by recombination-dependent DNA structures and/or replication-related sister chromatid junctions. RecQ helicases, including yeast Sgs1 and human BLM, have been implicated in both replication and recombination and protect genome integrity by preventing unscheduled mitotic recombination events. We have studied the RecQ helicase-mediated mechanisms controlling genome stability by analyzing replication forks encountering a damaged template in sgs1 cells. We show that, in sgs1 mutants, recombination-dependent cruciform structures accumulate at damaged forks. Their accumulation requires Rad51 protein, is counteracted by Srs2 DNA helicase, and does not prevent fork movement. Sgs1, but not Srs2, promotes resolution of these recombination intermediates. A functional Rad53 checkpoint kinase that is known to protect the integrity of the sister chromatid junctions is required for the accumulation of recombination intermediates in sgs1 mutants. Finally, top3 and top3 sgs1 mutants accumulate the same structures as sgs1 cells. We suggest that, in sgs1 cells, the unscheduled accumulation of Rad51-dependent cruciform structures at damaged forks result from defective maturation of recombination-dependent intermediates that originate from the replication-related sister chromatid junctions. Our findings might contribute to explaining some of the recombination defects of BLM cells.
[Keywords: Sgs1; RecQ helicases; DNA replication; recombination; checkpoint; Srs2]
Received August 21, 2004; revised version accepted December 3, 2004.
Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.322605.
3 These authors contributed equally to this work.
5 Corresponding author.
E-MAIL giordano.liberi{at}ifom-ieo-campus.it; FAX 39-02-574303231.
4 Present address: Institute of Cell Biology, ETH Hönggerberg, CH-8093 Zürich, Switzerland.
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