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Molecular and Cellular Biology, August 2005, p. 7226-7238, Vol. 25, No. 16
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.16.7226-7238.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Saccharomyces cerevisiae as a Model System To Define the Chromosomal Instability Phenotype{dagger}

Christopher D. Putnam, Vincent Pennaneach, and Richard D. Kolodner*

Ludwig Institute for Cancer Research, Departments of Medicine and Cellular and Molecular Medicine, and Cancer Center, University of California, San Diego School of Medicine, 9500 Gilman Drive, La Jolla, California 92093-0669

Received 15 March 2005/ Returned for modification 7 April 2005/ Accepted 3 May 2005

Translocations, deletions, and chromosome fusions are frequent events seen in cancers with genome instability. Here we analyzed 358 genome rearrangements generated in Saccharomyces cerevisiae selected by the loss of the nonessential terminal segment of chromosome V. The rearrangements appeared to be generated by both nonhomologous end joining and homologous recombination and targeted all chromosomes. Fifteen percent of the rearrangements occurred independently more than once. High levels of specific classes of rearrangements were isolated from strains with specific mutations: translocations to Ty elements were increased in telomerase-defective mutants, potential dicentric translocations and dicentric isochromosomes were associated with cell cycle checkpoint defects, chromosome fusions were frequent in strains with both telomerase and cell cycle checkpoint defects, and translocations to homolog genes were seen in strains with defects allowing homoeologous recombination. An analysis of human cancer-associated rearrangements revealed parallels to the effects that strain genotypes have on classes of rearrangement in S. cerevisiae.


* Corresponding author. Mailing address: Ludwig Institute for Cancer Research, University of California, San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0669. Phone: (858) 534-7802, ext. 7804. Fax: (858) 534-7750. E-mail: rkolodner{at}ucsd.edu.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.


Molecular and Cellular Biology, August 2005, p. 7226-7238, Vol. 25, No. 16
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.16.7226-7238.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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