A role for the MutL homologue MLH2 in controlling heteroduplex formation and in regulating between two different crossover pathways in budding yeast.
OBJECTIVE
Mismatch repair proteins play important roles during meiotic recombination in the budding yeast Saccharomyces cerevisiae and most eukaryotic organisms studied to date. To study the functions of the mismatch repair protein Mlh2p in meiosis, we constructed mlh2Delta strains and measured rates of crossing over, gene conversion, post-meiotic segregation and spore viability. We also analysed mlh1Delta, mlh3Delta, msh4Delta, msh5Delta, exo1Delta and mus81Delta mutant strains singularly and in various combinations.


RESULTS
Loss of MLH2 resulted in a small but significant decrease in spore viability and a significant increase in gene conversion frequencies but had no apparent effect on crossing over. Deletion of MLH2 in mlh3Delta, msh4Delta or msh5Delta strains resulted in significant proportion of the "lost" crossovers found in single deletion strains being regained in some genetic intervals. We and others propose that there are at least two pathways to generate crossovers in yeast (Ross-Macdonald and Roeder, 1994; Zalevsky et al., 1999; Khazanehdari and Borts, 2000; Novak et al., 2001; de los Santos et al., 2003). Most recombination intermediates are processed by the "major", Msh4-dependent pathway, which requires the activity of Mlh1p/Mlh3p/Msh4p/Msh5p as well as a number of other proteins. The minor pathway(s) utilizes Mms4p/Mus81p. We suggest that the absence of Mlh2p allows some crossovers from the MSH4 pathway to traverse the MUS81-dependent pathway.
Department of Genetics, University of Leicester, Leicester, UK.
M F F
MF
Abdullah
E R
ER
Hoffmann
V E
VE
Cotton
R H
RH
Borts
D048868:Adaptor Proteins, Signal Transducing; D000483:Alleles; D002470:Cell Survival; D020090:Chromosome Segregation / Q000235:genetics; D003434:Crossing Over, Genetic / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism; D005090:Exodeoxyribonucleases / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D005785:Gene Conversion / Q000235:genetics; D017353:Gene Deletion; D005838:Genotype; D008957:Models, Genetic; D000070957:MutL Protein Homolog 1; D000070956:MutL Proteins; D000074081:MutS Homolog 3 Protein; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009692:Nucleic Acid Heteroduplexes / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013172:Spores, Fungal / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C088859:MLH1 protein, S cerevisiae; C497822:MLH2 protein, S cerevisiae; C492408:MLH3 protein, S cerevisiae; C081696:MSH3 protein, S cerevisiae; C091158:MSH4 protein, S cerevisiae; C094801:MSH5 protein, S cerevisiae; D000074081:MutS Homolog 3 Protein; D009687:Nuclear Proteins; D009692:Nucleic Acid Heteroduplexes; D029701:Saccharomyces cerevisiae Proteins; D004720:Endonucleases; D005090:Exodeoxyribonucleases; C411624:MUS81 protein, S cerevisiae; C028450:exodeoxyribonuclease I; D000070957:MutL Protein Homolog 1; D000070956:MutL Proteins