| Title: | Homologous recombinational repair of double-strand breaks in yeast is enhanced by MAT heterozygosity through yKU-dependent and -independent mechanisms |
| Author(s): | Clikeman JA; Khalsa GJ; Barton SL; Nickoloff JA; |
| Address: | "Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA" |
| DOI: | 10.1093/genetics/157.2.579 |
| ISSN/ISBN: | 0016-6731 (Print) 0016-6731 (Linking) |
| Abstract: | "DNA double-strand breaks (DSBs) are repaired by homologous recombination (HR) and nonhomologous end-joining (NHEJ). NHEJ in yeast chromosomes has been observed only when HR is blocked, as in rad52 mutants or in the absence of a homologous repair template. We detected yKu70p-dependent imprecise NHEJ at a frequency of approximately 0.1% in HR-competent Rad+ haploid cells. Interestingly, yku70 mutation increased DSB-induced HR between direct repeats by 1.3-fold in a haploid strain and by 1.5-fold in a MAT homozygous (a/a) diploid, but yku70 had no effect on HR in a MAT heterozygous (a/alpha) diploid. yku70 might increase HR because it eliminates the competing precise NHEJ (religation) pathway and/or because yKu70p interferes directly or indirectly with HR. Despite the yku70-dependent increase in a/a cells, HR remained 2-fold lower than in a/alpha cells. Cell survival was also lower in a/a cells and correlated with the reduction in HR. These results indicate that MAT heterozygosity enhances DSB-induced HR by yKu-dependent and -independent mechanisms, with the latter mechanism promoting cell survival. Surprisingly, yku70 strains survived a DSB slightly better than wild type. We propose that this reflects enhanced HR, not by elimination of precise NHEJ since this pathway produces viable products, but by elimination of yKu-dependent interference of HR" |
| Keywords: | "Alleles *Antigens, Nuclear Cell Division DNA Damage/*genetics *DNA Helicases DNA Repair DNA-Binding Proteins/*genetics Diploidy Haploidy *Heterozygote Ku Autoantigen Mating Factor Models, Genetic Mutation Nuclear Proteins/*genetics Peptides/*genetics Plas;" |
| Notes: | "MedlineClikeman, J A Khalsa, G J Barton, S L Nickoloff, J A eng CA55302/CA/NCI NIH HHS/ Research Support, U.S. Gov't, P.H.S. 2001/02/07 Genetics. 2001 Feb; 157(2):579-89. doi: 10.1093/genetics/157.2.579" |
