The Role of the Mismatch Repair Machinery in Regulating Mitotic and Meiotic Recombination Between Diverged Sequences in Yeast

Corresponding author: Sue Jinks-Robertson, Department of Biology, 1510 Clifton Rd., Emory University, Atlanta, GA 30322., jinks{at}biology.emory.edu (E-mail)

Communicating editor: M. LICHTEN

Nonidentical recombination substrates recombine less efficiently than do identical substrates in yeast, and much of this inhibition can be attributed to action of the mismatch repair (MMR) machinery. In this study an intron-based inverted repeat assay system has been used to directly compare the rates of mitotic and meiotic recombination between pairs of 350-bp substrates varying from 82% to 100% in sequence identity. The recombination rate data indicate that sequence divergence impacts mitotic and meiotic recombination similarly, although subtle differences are evident. In addition to assessing recombination rates as a function of sequence divergence, the endpoints of mitotic and meiotic recombination events involving 94%-identical substrates were determined by DNA sequencing. The endpoint analysis indicates that the extent of meiotic heteroduplex DNA formed in a MMR-defective strain is 65% longer than that formed in a wild-type strain. These data are consistent with a model in which the MMR machinery interferes with the formation and/or extension of heteroduplex intermediates during recombination.

This article has been cited by other articles:

				C. Welz-Voegele and S. Jinks-Robertson Sequence Divergence Impedes Crossover More Than Noncrossover Events During Mitotic Gap Repair in Yeast Genetics, July 1, 2008; 179(3): 1251 - 1262. [Abstract] [Full Text] [PDF]

				J. E. Stone, R. G. Ozbirn, T. D. Petes, and S. Jinks-Robertson Role of Proliferating Cell Nuclear Antigen Interactions in the Mismatch Repair-Dependent Processing of Mitotic and Meiotic Recombination Intermediates in Yeast Genetics, March 1, 2008; 178(3): 1221 - 1236. [Abstract] [Full Text] [PDF]

				J. A. Smith, L. A. Bannister, V. Bhattacharjee, Y. Wang, B. C. Waldman, and A. S. Waldman Accurate Homologous Recombination Is a Prominent Double-Strand Break Repair Pathway in Mammalian Chromosomes and Is Modulated by Mismatch Repair Protein Msh2 Mol. Cell. Biol., November 15, 2007; 27(22): 7816 - 7827. [Abstract] [Full Text] [PDF]

				S. Sun and J. Xu Genetic Analyses of a Hybrid Cross Between Serotypes A and D Strains of the Human Pathogenic Fungus Cryptococcus neoformans Genetics, November 1, 2007; 177(3): 1475 - 1486. [Abstract] [Full Text] [PDF]

				R. L. Barnes and R. McCulloch Trypanosoma brucei homologous recombination is dependent on substrate length and homology, though displays a differential dependence on mismatch repair as substrate length decreases Nucleic Acids Res., May 11, 2007; 35(10): 3478 - 3493. [Abstract] [Full Text] [PDF]

				D. Yang, E. B. Goldsmith, Y. Lin, B. C. Waldman, V. Kaza, and A. S. Waldman Genetic Exchange Between Homeologous Sequences in Mammalian Chromosomes Is Averted by Local Homology Requirements for Initiation and Resolution of Recombination Genetics, September 1, 2006; 174(1): 135 - 144. [Abstract] [Full Text] [PDF]

				M. D. Yandeau-Nelson, Y. Xia, J. Li, M. G. Neuffer, and P. S. Schnable Unequal Sister Chromatid and Homolog Recombination at a Tandem Duplication of the a1 Locus in Maize Genetics, August 1, 2006; 173(4): 2211 - 2226. [Abstract] [Full Text] [PDF]

				A. Nicholson, R. M. Fabbri, J. W. Reeves, and G. F. Crouse The Effects of Mismatch Repair and RAD1 Genes on Interchromosomal Crossover Recombination in Saccharomyces cerevisiae Genetics, June 1, 2006; 173(2): 647 - 659. [Abstract] [Full Text] [PDF]

				T. Daikoku, A. Kudoh, Y. Sugaya, S. Iwahori, N. Shirata, H. Isomura, and T. Tsurumi Postreplicative Mismatch Repair Factors Are Recruited to Epstein-Barr Virus Replication Compartments J. Biol. Chem., April 21, 2006; 281(16): 11422 - 11430. [Abstract] [Full Text] [PDF]

				L. I. Khrustaleva, P. E. de Melo, A. W. van Heusden, and C. Kik The Integration of Recombination and Physical Maps in a Large-Genome Monocot Using Haploid Genome Analysis in a Trihybrid Allium Population Genetics, March 1, 2005; 169(3): 1673 - 1685. [Abstract] [Full Text] [PDF]

				T. Goldfarb and E. Alani Distinct Roles for the Saccharomyces cerevisiae Mismatch Repair Proteins in Heteroduplex Rejection, Mismatch Repair and Nonhomologous Tail Removal Genetics, February 1, 2005; 169(2): 563 - 574. [Abstract] [Full Text] [PDF]

				M. D. Yandeau-Nelson, Q. Zhou, H. Yao, X. Xu, B. J. Nikolau, and P. S. Schnable MuDR Transposase Increases the Frequency of Meiotic Crossovers in the Vicinity of a Mu Insertion in the Maize a1 Gene Genetics, February 1, 2005; 169(2): 917 - 929. [Abstract] [Full Text] [PDF]

				R. M. Spell and S. Jinks-Robertson Examination of the Roles of Sgs1 and Srs2 Helicases in the Enforcement of Recombination Fidelity in Saccharomyces cerevisiae Genetics, December 1, 2004; 168(4): 1855 - 1865. [Abstract] [Full Text] [PDF]

				R. Opperman, E. Emmanuel, and A. A. Levy The Effect of Sequence Divergence on Recombination Between Direct Repeats in Arabidopsis Genetics, December 1, 2004; 168(4): 2207 - 2215. [Abstract] [Full Text] [PDF]

				N. Sugawara, T. Goldfarb, B. Studamire, E. Alani, and J. E. Haber Heteroduplex rejection during single-strand annealing requires Sgs1 helicase and mismatch repair proteins Msh2 and Msh6 but not Pms1 PNAS, June 22, 2004; 101(25): 9315 - 9320. [Abstract] [Full Text] [PDF]

				J. G. Jelesko, K. Carter, W. Thompson, Y. Kinoshita, and W. Gruissem Meiotic Recombination Between Paralogous RBCSB Genes on Sister Chromatids of Arabidopsis thaliana Genetics, February 1, 2004; 166(2): 947 - 957. [Abstract] [Full Text] [PDF]

				R. M. Spell and S. Jinks-Robertson Role of Mismatch Repair in the Fidelity of RAD51- and RAD59-Dependent Recombination in Saccharomyces cerevisiae Genetics, December 1, 2003; 165(4): 1733 - 1744. [Abstract] [Full Text] [PDF]

				R. V. Abdelnoor, R. Yule, A. Elo, A. C. Christensen, G. Meyer-Gauen, and S. A. Mackenzie Substoichiometric shifting in the plant mitochondrial genome is influenced by a gene homologous to MutS PNAS, May 13, 2003; 100(10): 5968 - 5973. [Abstract] [Full Text] [PDF]

				J. M. Stark and M. Jasin Extensive Loss of Heterozygosity Is Suppressed during Homologous Repair of Chromosomal Breaks Mol. Cell. Biol., January 15, 2003; 23(2): 733 - 743. [Abstract] [Full Text] [PDF]

				C. Welz-Voegele, J. E. Stone, P. T. Tran, H. M. Kearney, R. M. Liskay, T. D. Petes, and S. Jinks-Robertson Alleles of the Yeast PMS1 Mismatch-Repair Gene That Differentially Affect Recombination- and Replication-Related Processes Genetics, November 1, 2002; 162(3): 1131 - 1145. [Abstract] [Full Text] [PDF]

				S. J. Raynard and M. D. Baker Incorporation of Large Heterologies Into Heteroduplex DNA During Double-Strand-Break Repair in Mouse Cells Genetics, October 1, 2002; 162(2): 977 - 985. [Abstract] [Full Text] [PDF]

				J. A. Birdsell Integrating Genomics, Bioinformatics, and Classical Genetics to Study the Effects of Recombination on Genome Evolution Mol. Biol. Evol., July 1, 2002; 19(7): 1181 - 1197. [Abstract] [Full Text] [PDF]

				G. P. Copenhaver, E. A. Housworth, and F. W. Stahl Crossover Interference in Arabidopsis Genetics, April 1, 2002; 160(4): 1631 - 1639. [Abstract] [Full Text] [PDF]

				C. Allen, A. Kurimasa, M. A. Brenneman, D. J. Chen, and J. A. Nickoloff DNA-dependent protein kinase suppresses double-strand break-induced and spontaneous homologous recombination PNAS, March 19, 2002; 99(6): 3758 - 3763. [Abstract] [Full Text] [PDF]

				C.-G. Gendrel and M. Dutreix (CA/TG) Microsatellite Sequences Escape the Inhibition of Recombination by Mismatch Repair in Saccharomyces cerevisiae Genetics, December 1, 2001; 159(4): 1539 - 1545. [Abstract] [Full Text] [PDF]

				Y. Li, J. P. Bernot, C. Illingworth, W. Lison, K. M. Bernot, W. B. Eggleston, K. J. Fogle, J. E. DiPaola, J. Kermicle, and M. Alleman Gene Conversion Within Regulatory Sequences Generates Maize r Alleles With Altered Gene Expression Genetics, December 1, 2001; 159(4): 1727 - 1740. [Abstract] [Full Text] [PDF]

				P. Pichierri, A. Franchitto, R. Piergentili, C. Colussi, and F. Palitti Hypersensitivity to camptothecin in MSH2 deficient cells is correlated with a role for MSH2 protein in recombinational repair Carcinogenesis, November 1, 2001; 22(11): 1781 - 1787. [Abstract] [Full Text] [PDF]

				H. M. Kearney, D. T. Kirkpatrick, J. L. Gerton, and T. D. Petes Meiotic Recombination Involving Heterozygous Large Insertions in Saccharomyces cerevisiae: Formation and Repair of Large, Unpaired DNA Loops Genetics, August 1, 2001; 158(4): 1457 - 1476. [Abstract] [Full Text] [PDF]

				P. T. Tran, J. A. Simon, and R. M. Liskay Interactions of Exo1p with components of MutLalpha in Saccharomyces cerevisiae PNAS, July 24, 2001; (2001) 161175998. [Abstract] [Full Text] [PDF]

				B. Elliott and M. Jasin Repair of Double-Strand Breaks by Homologous Recombination in Mismatch Repair-Defective Mammalian Cells Mol. Cell. Biol., April 15, 2001; 21(8): 2671 - 2682. [Abstract] [Full Text]

				J. A. Clikeman, S. L. Wheeler, and J. A. Nickoloff Efficient Incorporation of Large (>2 kb) Heterologies Into Heteroduplex DNA: Pms1/Msh2-Dependent and -Independent Large Loop Mismatch Repair in Saccharomyces cerevisiae Genetics, April 1, 2001; 157(4): 1481 - 1491. [Abstract] [Full Text]

				Q. Chen, A. Ijpma, and C. W. Greider Two Survivor Pathways That Allow Growth in the Absence of Telomerase Are Generated by Distinct Telomere Recombination Events Mol. Cell. Biol., March 1, 2001; 21(5): 1819 - 1827. [Abstract] [Full Text]

				R. Friedman and A. L. Hughes Gene Duplication and the Structure of Eukaryotic Genomes Genome Res., March 1, 2001; 11(3): 373 - 381. [Abstract] [Full Text]

				C. H. Langley, B. P. Lazzaro, W. Phillips, E. Heikkinen, and J. M. Braverman Linkage Disequilibria and the Site Frequency Spectra in the su(s) and su(wa) Regions of the Drosophila melanogaster X Chromosome Genetics, December 1, 2000; 156(4): 1837 - 1852. [Abstract] [Full Text]

				E. Evans and E. Alani Roles for Mismatch Repair Factors in Regulating Genetic Recombination Mol. Cell. Biol., November 1, 2000; 20(21): 7839 - 7844. [Full Text]

				P. T. Tran and R. M. Liskay Functional Studies on the Candidate ATPase Domains of Saccharomyces cerevisiae MutLalpha Mol. Cell. Biol., September 1, 2000; 20(17): 6390 - 6398. [Abstract] [Full Text]

				A. J. R. Bishop, E. J. Louis, and R. H. Borts Minisatellite Variants Generated in Yeast Meiosis Involve DNA Removal During Gene Conversion Genetics, September 1, 2000; 156(1): 7 - 20. [Abstract] [Full Text]

				A. Nicholson, M. Hendrix, S. Jinks-Robertson, and G. F. Crouse Regulation of Mitotic Homeologous Recombination in Yeast: Functions of Mismatch Repair and Nucleotide Excision Repair Genes Genetics, January 1, 2000; 154(1): 133 - 146. [Abstract] [Full Text]

				J. Wu, L. Gu, H. Wang, N. E. Geacintov, and G.-M. Li Mismatch Repair Processing of Carcinogen-DNA Adducts Triggers Apoptosis Mol. Cell. Biol., December 1, 1999; 19(12): 8292 - 8301. [Abstract] [Full Text] [PDF]

				J. A. Nickoloff, D. B. Sweetser, J. A. Clikeman, G. J. Khalsa, and S. L. Wheeler Multiple Heterologies Increase Mitotic Double-Strand Break-Induced Allelic Gene Conversion Tract Lengths in Yeast Genetics, October 1, 1999; 153(2): 665 - 679. [Abstract] [Full Text] [PDF]

				A. Fabisiewicz and L. Worth Jr. Escherichia coli MutS,L Modulate RuvAB-dependent Branch Migration between Diverged DNA J. Biol. Chem., March 16, 2001; 276(12): 9413 - 9420. [Abstract] [Full Text] [PDF]

				P. T. Tran, J. A. Simon, and R. M. Liskay Interactions of Exo1p with components of MutLalpha in Saccharomyces cerevisiae PNAS, August 14, 2001; 98(17): 9760 - 9765. [Abstract] [Full Text] [PDF]