Suppression of genome instability by redundant S-phase checkpoint pathways in Saccharomyces cerevisiae

Proceedings of the National Academy of Sciences of the United States of America
Kyungjae Myung, Richard D Kolodner

Abstract

Cancer cells show increased genome rearrangements, although it is unclear what defects cause these rearrangements. Previous studies have implicated the Saccharomyces cerevisiae replication checkpoint in the suppression of spontaneous genome rearrangements. In the present study, low doses of methyl methane sulfonate that activate the intra-S checkpoint but not the G1 or G2 DNA damage checkpoints were found to cause increased accumulation of genome rearrangements in both wild-type strains and to an even greater extent in strains containing mutations causing defects in the intra-S checkpoint. The rearrangements were primarily translocations or events resulting in deletion of a portion of a chromosome arm along with the addition of a new telomere. Combinations of mutations causing individual defects in the RAD24 or SGS1 branches of the intra-S checkpoint or the replication checkpoint showed synergistic interactions with regard to the spontaneous genome instability rate. PDS1 and the RAD50-MRE11-XRS2 complex were found to be important members of all the S-phase checkpoints in suppressing genome instability, whereas RAD53 only seemed to play a role in the intra-S checkpoints. Combinations of mutations that seem to result in inactivat...Continue Reading

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Citations

Aug 30, 2003·Trends in Cell Biology·Rakesh R KhakharSusan M Gasser
Jan 28, 2003·DNA Repair·Kyungjae Myung, Richard D Kolodner
Jan 30, 2008·Nature Reviews. Genetics·Andrés Aguilera, Belén Gómez-González
Oct 2, 2004·Nature Reviews. Molecular Cell Biology·Jiri BartekJiri Lukas
Nov 26, 2010·Proceedings of the National Academy of Sciences of the United States of America·Salma KaocharTed Weinert
Aug 29, 2006·Nucleic Acids Research·Jennifer A Cobb, Lotte Bjergbaek
Dec 28, 2002·Genes & Development·Kenji ShimadaSusan M Gasser
Aug 29, 2003·Molecular and Cellular Biology·Charly ChahwanNicholas Rhind
Aug 2, 2005·Molecular and Cellular Biology·Christopher D PutnamRichard D Kolodner
Feb 2, 2006·Molecular and Cellular Biology·Akira MotegiKyungjae Myung
May 15, 2010·Cell Division·Jorrit M Enserink, Richard D Kolodner
Aug 17, 2010·PloS One·Kristina H SchmidtAaron Rubenstein
Oct 2, 2013·BioMed Research International·Annapaola Franchitto
May 17, 2003·Proceedings of the National Academy of Sciences of the United States of America·Kyungjae MyungRichard D Kolodner
Oct 30, 2004·Proceedings of the National Academy of Sciences of the United States of America·Kyungjae MyungRichard D Kolodner
Aug 26, 2004·Proceedings of the National Academy of Sciences of the United States of America·Christopher D PutnamRichard D Kolodner
Dec 12, 2002·Proceedings of the National Academy of Sciences of the United States of America·Francis FabreSerge Gangloff
Sep 10, 2003·Proceedings of the National Academy of Sciences of the United States of America·Piotr A MieczkowskiThomas D Petes
Feb 1, 2006·Proceedings of the National Academy of Sciences of the United States of America·Soma BanerjeeKyungjae Myung
Jun 9, 2004·Proceedings of the National Academy of Sciences of the United States of America·Stephanie SmithKyungjaem Myung

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