title: Saccharomyces cerevisiae exonuclease-1 plays a role in UV resistance that is distinct from nucleotide excision repair.
abstract: Two closely related genes, EXO1 and DIN 7, in the budding yeast Saccharomyces cerevisiae have been found to be sequence homologs of the exo1 gene from the fission yeast Schizosaccharomyces pombe . The proteins encoded by these genes belong to the Rad2/XPG and Rad27/FEN-1 families, which are structure-specific nucleases functioning in DNA repair. An XPG nuclease deficiency in humans is one cause of xeroderma pigmentosum and those afflicted display a hypersensitivity to UV light. Deletion of the RAD2 gene in S. cerevisiae also causes UV hypersensitivity, due to a defect in nucleotide excision repair (NER), but residual UV resistance remains. In this report, we describe evidence for the residual repair of UV damage to DNA that is dependent upon Exo1 nuclease. Expression of the EXO1 gene is UV inducible. Genetic analysis indicates that the EXO1 gene is involved in a NER-independent pathway for UV repair, as exo1 rad2 double mutants are more sensitive to UV than either the rad2 or exo1 single mutants. Since the roles of EXO1 in mismatch repair and recombination have been established, double mutants were constructed to examine the possible relationship between the role of EXO1 in UV resistance and its roles in other pathways for repair of UV damaged DNA. The exo1 msh2 , exo1 rad51 , rad2 rad51 and rad2 msh2 double mutants were all more sensitive to UV than their respective pairs of single mutants. This suggests that the observed UV sensitivity of the exo1 deletion mutant is unlikely to be due to its functional deficiencies in MMR, recombination or NER. Further, it suggests that the EXO1 , RAD51 and MSH2 genes control independent mechanisms for the maintenance of UV resistance.
authors.affiliation: Department of Cell and Tumor Biology, The Beckman Research Institute of City of Hope, Duarte, CA 91010-3000, USA.
authors.forename: J
authors.initials: J
authors.lastname: Qiu
authors.forename: M X
authors.initials: MX
authors.lastname: Guan
authors.forename: A M
authors.initials: AM
authors.lastname: Bailis
authors.forename: B
authors.initials: B
authors.lastname: Shen
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D017931:DNA Primers; D004260:DNA Repair; D004843:Epistasis, Genetic; D005090:Exodeoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000528:radiation effects; D015966:Gene Expression Regulation, Fungal / Q000528:radiation effects; D008969:Molecular Sequence Data; D011836:Radiation Tolerance; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces / Q000201:enzymology; D017386:Sequence Homology, Amino Acid; D014466:Ultraviolet Rays
chemical_list: D017931:DNA Primers; D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; C105071:DIN7 protein, S cerevisiae; D005090:Exodeoxyribonucleases; C028450:exodeoxyribonuclease I