Control of GT Repeat Stability in Schizosaccharomyces pombe by Mismatch Repair Factors

Corresponding author: Oliver Fleck, Institute of Cell Biology, University of Bern, Baltzer-Strasse 4, CH-3012 Bern, Switzerland., fleck{at}izb.unibe.ch (E-mail)

Communicating editor: M. LICHTEN

The mismatch repair (MMR) system ensures genome integrity by removing mispaired and unpaired bases that originate during replication. A major source of mutational changes is strand slippage in repetitive DNA sequences without concomitant repair. We established a genetic assay that allows measuring the stability of GT repeats in the ade6 gene of Schizosaccharomyces pombe. In repair-proficient strains most of the repeat variations were insertions, with addition of two nucleotides being the most frequent event. GT repeats were highly destabilized in strains defective in msh2 or pms1. In these backgrounds, mainly 2-bp insertions and 2-bp deletions occurred. Surprisingly, essentially the same high mutation rate was found with mutants defective in msh6. In contrast, a defect in swi4 (a homologue of Msh3) caused only slight effects, and instability was not further increased in msh6 swi4 double mutants. Also inactivation of exo1, which encodes an exonuclease that has an MMR-dependent function in repair of base-base mismatches, caused only slightly increased repeat instability. We conclude that Msh2, Msh6, and Pms1 have an important role in preventing tract length variations in dinucleotide repeats. Exo1 and Swi4 have a minor function, which is at least partially independent of MMR.

This article has been cited by other articles:

				G.-F. Richard, A. Kerrest, and B. Dujon Comparative Genomics and Molecular Dynamics of DNA Repeats in Eukaryotes Microbiol. Mol. Biol. Rev., December 1, 2008; 72(4): 686 - 727. [Abstract] [Full Text] [PDF]

				T. Yamada-Inagawa, A. J. S. Klar, and J. Z. Dalgaard Schizosaccharomyces pombe Switches Mating Type by the Synthesis-Dependent Strand-Annealing Mechanism Genetics, September 1, 2007; 177(1): 255 - 265. [Abstract] [Full Text] [PDF]

				K. M. Doherty, S. Sharma, L. A. Uzdilla, T. M. Wilson, S. Cui, A. Vindigni, and R. M. Brosh Jr. RECQ1 Helicase Interacts with Human Mismatch Repair Factors That Regulate Genetic Recombination J. Biol. Chem., July 29, 2005; 280(30): 28085 - 28094. [Abstract] [Full Text] [PDF]

				C. Holmberg, O. Fleck, H. A. Hansen, C. Liu, R. Slaaby, A. M. Carr, and O. Nielsen Ddb1 controls genome stability and meiosis in fission yeast Genes & Dev., April 1, 2005; 19(7): 853 - 862. [Abstract] [Full Text] [PDF]

				S. Estes, P. C. Phillips, D. R. Denver, W. K. Thomas, and M. Lynch Mutation Accumulation in Populations of Varying Size: The Distribution of Mutational Effects for Fitness Correlates in Caenorhabditis elegans Genetics, March 1, 2004; 166(3): 1269 - 1279. [Abstract] [Full Text] [PDF]

				C. Tornier, S. Bessone, I. Varlet, C. Rudolph, M. Darmon, and O. Fleck Requirement for Msh6, but Not for Swi4 (Msh3), in Msh2-Dependent Repair of Base-Base Mismatches and Mononucleotide Loops in Schizosaccharomyces pombe Genetics, May 1, 2001; 158(1): 65 - 75. [Abstract] [Full Text]

				M. Hohl, O. Christensen, C. Kunz, H. Naegeli, and O. Fleck Binding and Repair of Mismatched DNA Mediated by Rhp14, the Fission Yeast Homologue of Human XPA J. Biol. Chem., August 10, 2001; 276(33): 30766 - 30772. [Abstract] [Full Text] [PDF]