Journal article
The rad52-Y66A allele alters the choice of donor template during spontaneous chromosomal recombination
Spontaneous mitotic recombination is a potential source of genetic changes Such as loss of heterozygosity and chromosome translocations, which may lead to genetic disease. In this study we have used a rad52 hyper-recombination mutant, rad52-Y66A, to investigate the process of spontaneous heteroallelic recombination in the yeast Soccharomyces cerevisiae.
We find that spontaneous recombination has different genetic requirements, depending on whether the recombination event occurs between chromosomes or between chromosome and plasmid sequences. The hyper-recombination phenotype of the rad52-Y66A mutation is epistatic with deletion of MRE11, which is required for establishment of DNA damage-induced cohesion.
Moreover, single-cell analysis of strains expressing YFP-tagged Rad52-Y66A reveals a close to wild-type frequency of focus formation, but with foci lasting 6 times longer. This result suggests that spontaneous DNA lesions that require recombinational repair occur at the same frequency in wild-type and rad52-Y66A cells, but that the recombination process is slow in rad52-Y66A cells.
Taken together, we propose that the slow recombinational DNA repair in the rad52-Y66A mutant leads to a by-pass of the window-of-opportunity for sister chromatid recombination normally promoted by MRE11-dependent damage-induced cohesion thereby causing a shift towards interchromosomal recombination.
Language: | English |
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Year: | 2010 |
Pages: | 23-32 |
ISSN: | 15687856 and 15687864 |
Types: | Journal article |
DOI: | 10.1016/j.dnarep.2009.10.001 |
ORCIDs: | 0000-0002-4830-5247 and Mortensen, Uffe Hasbro |
Alleles Chromosomes, Fungal DNA Damage DNA Repair DNA, Fungal Endodeoxyribonucleases Exodeoxyribonucleases MRE11 protein, S cerevisiae Mutation RAD52 protein, S cerevisiae Rad52 DNA Repair and Recombination Protein Recombination, Genetic Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins Templates, Genetic