High impact information on RAD59

• Overexpression of RAD52 was found to suppress the DNA repair and recombination defects conferred by the rad59 mutation, suggesting that these proteins have overlapping roles or function as a complex [1].
• One mutation identified, rad59, reduced recombination 1200-fold in the presence of a rad51 mutation, but only 4- to 5-fold in a wild-type background [1].
• The rad59 mutant strain was sensitive to ionizing radiation, and this phenotype was used to clone the RAD59 gene by complementation [1].
• However, the rate of interchromosomal recombination was increased in a rad59 homozygous diploid [1].
• We found that Rad59p plays a role in removing nonhomologous sequences from the ends of single-stranded DNA when it invades a homologous DNA template, in a manner similar to that previously seen with srs2 mutants [2].

Biological context of RAD59

• Such a mechanism of recombination is RAD1-RAD59-dependent and yields gene conversions highly associated with the inversion of the repeat [3].
• The RAD59 gene product also participates in the RAD1-dependent pathway of recombination between direct repeats [4].
• A mutant with a deletion of RAD59, a homologue of RAD52, was defective for SSA, especially when the homologous-sequence length was short; however, even with 1.17-kb substrates, SSA was reduced fourfold [2].
• The differences between the RAD51- and RAD50/RAD59-dependent pathways account for the distinct ways that two different recombination processes maintain yeast telomeres in the absence of telomerase [5].
• Plasmid gap repair was reduced synergistically in rad51 rad59 double mutants, indicating an important role for RAD59 in RAD51-independent repair [6].

Physical interactions of RAD59

• The yeast recombinational repair protein Rad59 interacts with Rad52 and stimulates single-strand annealing [7].
• A novel yeast mutation, rad52-L89F, causes a specific defect in Rad51-independent recombination that correlates with a reduced ability of Rad52-L89F to interact with Rad59 [8].

Other interactions of RAD59

• In the budding yeast Saccharomyces cerevisiae, the RAD52 gene is essential for all homologous recombination events and its homologue, the RAD59 gene, is important for those that occur independently of RAD51 [9].
• In addition, the regulation of homeologous recombination in rad51 and rad59 mutants displayed distinct patterns of inhibition by different members of the MMR pathway [10].
• RAD50 and RAD59, genes required for BIR, are required for X-ray-associated SCE but not for SCE stimulated by HO-induced DSBs [11].

Analytical, diagnostic and therapeutic context of RAD59

• Similarly, using electrophoretic mobility shift assays, we found the affinity of both Rad52 and Rad59 proteins for DNA ends to be comparable with their affinity for internal sequences [12].
• Here we demonstrate physical interaction between Rad52 and Rad59 using the yeast two-hybrid system and co-immunoprecipitation from yeast extracts [7].
• We have studied the functional overlap between Rad52 and Rad59 in living cells using chimeras of the two proteins and site-directed mutagenesis [13].

References