Differential Mismatch Repair Can Explain the Disproportionalities Between Physical Distances and Recombination Frequencies of cyc1 Mutations in Yeast

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Differential Mismatch Repair Can Explain the Disproportionalities Between Physical Distances and Recombination Frequencies of cyc1 Mutations in Yeast

C. W. Moore, D. M. Hampsey, J. F. Ernst and F. Sherman
Department of Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642 Present address: City University of New York Medical School, Department of Microbiology, Science/Marshak Building, 138th Street at Covent Avenue, New York, New York 10031.

Recombination rates have been examined in two-point crosses of various defined cyc1 mutations that cause the loss or nonfunction of iso-1-cytochrome c in the yeast Saccharomyces cerevisiae. Recombinants arising by three different means were investigated, including X-ray induced mitotic recombination, spontaneous mitotic recombination, and meiotic recombination. Heteroallelic diploid strains were derived by crossing cyc1 mutants containing a series of alterations at or near the same site to cyc1 mutants containing alterations at variouis distances. Marked disproportionalities between physical distances and recombination frequencies were observed with certain cyc1 mutations, indicating that certain mismatched bases can significantly affect recombination. The marker effects were more pronounced when the two mutational sites of the heteroalleles were within about 20 base pairs, but separated by at least 4 base pairs. Two alleles, cyc1-163 and cyc1-166, which arose by G{middot}C->C{middot}G transversions at nucleotide positions 3 and 194, respectively, gave rise to especially high rates of recombination. Other mutations having different substitutions at the same nucleotide positions were not associated with abnormally high recombination frequencies. We suggest that these marker effects are due to the lack of repair of either G/G or C/C mismatched base pairs, while the other mismatched base pair of the heteroallele undergoes substantial repair. Furthermore, we suggest that diminished recombination frequencies are due to the concomitant repair of both mismatches within the same DNA tract.

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