Msh2 blocks an alternative mechanism for non-homologous tail removal during single-strand annealing in Saccharomyces cerevisiae.
Chromosomal translocations are frequently observed in cells exposed to agents that cause DNA double-strand breaks (DSBs), such as ionizing radiation and chemotherapeutic drugs, and are often associated with tumors in mammals. Recently, translocation formation in the budding yeast, Saccharomyces cerevisiae, has been found to occur at high frequencies following the creation of multiple DSBs adjacent to repetitive sequences on non-homologous chromosomes. The genetic control of translocation formation and the chromosome complements of the clones that contain translocations suggest that translocation formation occurs by single-strand annealing (SSA). Among the factors important for translocation formation by SSA is the central mismatch repair (MMR) and homologous recombination (HR) factor, Msh2. Here we describe the effects of several msh2 missense mutations on translocation formation that suggest that Msh2 has separable functions in stabilizing annealed single strands, and removing non-homologous sequences from their ends. Additionally, interactions between the msh2 alleles and a null allele of RAD1, which encodes a subunit of a nuclease critical for the removal of non-homologous tails suggest that Msh2 blocks an alternative mechanism for removing these sequences. These results suggest that Msh2 plays multiple roles in the formation of chromosomal translocations following acute levels of DNA damage.
Manthey
Glenn M
GM
Division of Molecular Biology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California, United States of America.
Naik
Nilan
N
Bailis
Adam M
AM
D000483:Alleles; D002384:Catalysis; D004249:DNA Damage; D004260:DNA Repair; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D004171:Diploidy; D004843:Epistasis, Genetic; D006579:Heterozygote; D008954:Models, Biological; D051718:MutS Homolog 2 Protein / Q000235:genetics* / Q000502:physiology*; D020125:Mutation, Missense; D010641:Phenotype; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D014178:Translocation, Genetic
D029701:Saccharomyces cerevisiae Proteins; C530845:HO protein, S cerevisiae; D015252:Deoxyribonucleases, Type II Site-Specific; C489751:MSH2 protein, S cerevisiae; D051718:MutS Homolog 2 Protein