Disease relevance of RAD1

• The collected experiments reveal a profound toxicity of strand breaks with irreparable 3' blocking lesions, and extend the function of the Rad1/Rad10 salvage pathway to 3'-phosphates [1].
• None of the mutants demonstrated appreciable change in sensitivity to JM216 presumably as a consequence of a lack of resistance of the wild-type strain, whereas a moderate increase in sensitivity to JM335 was observed for most of the mutants, and hypersensitivity to BBR3464 was observed only in rad1 and -3 [2].

High impact information on RAD1

• By examining the PMS patterns in yeast strains heterozygous for a mutant allele with a 26-base-pair insertion, we find that the repair of 26-base loops involves Msh2 (a DNA-mismatch repair protein) and Rad1 (a protein required for nucleotide-excision repair) [3].
• Chromosome XVI was the last yeast chromosome identified, and some of the genes mapped early to it, such as GAL4, PEP4 and RAD1 (ref. 2) have played important roles in the development of yeast biology [4].
• In Saccharomyces cerevisiae, of the many genes required for excision repair of ultraviolet-damaged DNA, only RAD1 and RAD10 also function in genetic recombination [5].
• Furthermore, these data suggest that Rad1-Rad10 endonuclease incises DNA 5' to damaged bases during nucleotide excision repair [6].
• Although rad1 mutants are resistant to x-rays and can complete DSB-mediated mating-type switching, they could not complete recombination when the ends of the break contained approximately 60 base pairs of nonhomology [7].

Biological context of RAD1

• RAD1, an excision repair gene of Saccharomyces cerevisiae, is also involved in recombination [8].
• In this paper, we report our observations on the effect of the RAD1 gene on genetic recombination [8].
• In Saccharomyces cerevisiae, the RAD1 and RAD10 genes are involved in DNA nucleotide excision repair (NER) and in a pathway of mitotic recombination that occurs between direct repeat DNA sequences [9].
• Dependence on RAD52 and RAD1 for anticancer drug resistance mediated by inactivation of mismatch repair genes [10].
• Double strand break-induced plasmid integration was also decreased by disruption of RAD10, which forms a complex with RAD1; disruption of RAD4 had no effect [11].

Anatomical context of RAD1

• Using the 'two-hybrid' genetic assay system we now report that Rad1 and Rad10 proteins are subunits of a specific complex in the cell nucleus [12].
• (4) Leaky alleles of rad1, rad3 and rad14 show a very marked difference in repair rates of the two lesions, rather like the human XPA revertant cell line XP129 and the Chinese hamster mutants UV61 and V-H1 [13].

Associations of RAD1 with chemical compounds

• The source of these phosphates remains enigmatic, however, because apn1 tpp1 rad1 slow growth could be correlated with neither the presence of a yeast delta-lyase, the activity of the 3'-phosphate-generating enzyme Tdp1, nor levels of endogenous oxidation [1].
• The yeast RAD2, but not RAD1, gene is involved in the transcription-coupled repair of thymine glycols [14].
• By hydroxylamine mutagenesis, we have identified a rad1 mutant allele whose encoded protein fails to complex with RAD10 [15].
• The inactivation of Rad1 or Rad10 in GCR mutator strains also slightly enhanced methyl methanesulfonate sensitivity [16].
• Deleting uracil glycosylase suppressed both tpp1 apn1 rad1 and apn1 apn2 rad1 growth defects by reducing the abasic site burden [17].

Physical interactions of RAD1

• The RAD1/RAD10 complex is highly stable, being refractory to 1 M NaCl and to low concentrations of SDS [15].
• Studies on rad1 delta rad52-8 strains show that these mutations interact synergistically in the presence or absence of HOT1, resulting in low levels of recombination [18].

Other interactions of RAD1

• In fact, apn1 apn2 rad1 triple mutants can form microcolonies of approximately 300 cells [19].
• RAD10, an excision repair gene of Saccharomyces cerevisiae, is involved in the RAD1 pathway of mitotic recombination [20].
• In Saccharomyces cerevisiae, RAD1 and RAD52 are required for alternate pathways of mitotic recombination [21].
• These results suggest that a RAD1-dependent function is involved in the processing of damaged DNA that results from the loss of Top3 activity, targeting such DNA for repair by recombination [22].
• Removal of one nonhomologous DNA end during gene conversion by a RAD1- and MSH2-independent pathway [23].

Analytical, diagnostic and therapeutic context of RAD1

• By means of genetic crosses, apn1 apn2 rad1 x quadruple mutants are generated [24].
• Molecular cloning and nucleotide sequence analysis of the Saccharomyces cerevisiae RAD1 gene [25].
• We characterize the RAD1/RAD10 endonuclease activity on both single-stranded and double-stranded DNAs, using agarose gel electrophoresis and trichloroacetic acid precipitation [26].
• By several independent criteria, including co-purification, immunoprecipitation, and gel filtration of homogeneous proteins, we show that the damage recognition factor Rad14 exists in a ternary complex with the Rad1-Rad10 nuclease [27].
• A Neurospora crassa gene encoding a product with homology to the Saccharomyces cerevisiae Rad1 nucleotide excision repair (NER) protein was isolated by degenerate PCR [28].

References