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Molecular and Cellular Biology, July 2006, p. 5406-5420, Vol. 26, No. 14
0270-7306/06/$08.00+0     doi:10.1128/MCB.00161-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Control of Translocations between Highly Diverged Genes by Sgs1, the Saccharomyces cerevisiae Homolog of the Bloom's Syndrome Protein

Kristina H. Schmidt,1,2* Joann Wu,1 and Richard D. Kolodner1

Ludwig Institute for Cancer Research, Departments of Medicine and Cellular and Molecular Medicine, and Cancer Center, University of California San Diego, School of Medicine, La Jolla, California 92093,1 Department of Biology, University of South Florida, 4202 E. Fowler Avenue, SCA110, Tampa, Florida 336202

Received 27 January 2006/ Returned for modification 24 February 2006/ Accepted 28 April 2006

Sgs1 is a RecQ family DNA helicase required for genome stability in Saccharomyces cerevisiae whose human homologs BLM, WRN, and RECQL4 are mutated in Bloom's, Werner, and Rothmund Thomson syndromes, respectively. Sgs1 and mismatch repair (MMR) are inhibitors of recombination between similar but divergent (homeologous) DNA sequences. Here we show that SGS1, but not MMR, is critical for suppressing spontaneous, recurring translocations between diverged genes in cells with mutations in the genes encoding the checkpoint proteins Mec3, Rad24, Rad9, or Rfc5, the chromatin assembly factors Cac1 or Asf1, and the DNA helicase Rrm3. The S-phase checkpoint kinase and telomere maintenance factor Tel1, a homolog of the human ataxia telangiectasia (ATM) protein, prevents these translocations, whereas the checkpoint kinase Mec1, a homolog of the human ATM-related protein, and the Rad53 checkpoint kinase are not required. The translocation structures observed suggest involvement of a dicentric intermediate and break-induced replication with multiple cycles of DNA template switching.


* Corresponding author. Mailing address: Department of Biology, University of South Florida, 4202 E. Fowler Avenue, SCA110, Tampa, FL 33620. Phone: (813) 974-1592. Fax: (813) 974-3263. E-mail: kschmidt{at}cas.usf.edu.


Molecular and Cellular Biology, July 2006, p. 5406-5420, Vol. 26, No. 14
0270-7306/06/$08.00+0     doi:10.1128/MCB.00161-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




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