title: Human SNM1A suppresses the DNA repair defects of yeast pso2 mutants.
abstract: Pso2/Snm1 plays a key role in the repair of DNA interstrand cross-links in yeast. Human cells possess three orthologues of Pso2; SNM1A, SNM1B/Apollo and SNM1C/Artemis. Studies using mammalian cells disrupted or depleted for these genes have yielded equivocal evidence that any of these is a true functional homologues of the yeast gene. Here we show that ectopic expression of only one of the three human orthologues, hSNM1A, effectively suppresses the sensitivity of yeast pso2 (snm1) disruptants to cross-linking agents. Two other phenotypes of the pso2 mutants are also partially rescued by ectopic expression of hSNM1A, namely the double-strand repair break defect observed during cross-link processing in pso2 cells, as well as the spontaneous intrachromatid recombination defect of pso2 msh2 double mutants. Finally, we show that recombinant hSNM1A is a 5'-exonuclease, as also recently reported for the yeast Pso2 protein. Together our data suggest that hSnm1A is a functional homologue of yeast Pso2/Snm1.
authors.affiliation: Cancer Research UK Drug-DNA Interactions Research Group, Department of Oncology, UCL Medical School, London, UK.
authors.forename: Ali
authors.initials: A
authors.lastname: Hazrati
authors.forename: Marc
authors.initials: M
authors.lastname: Ramis-Castelltort
authors.forename: Sovan
authors.initials: S
authors.lastname: Sarkar
authors.forename: Louise J
authors.initials: LJ
authors.lastname: Barber
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Schofield
authors.forename: John A
authors.initials: JA
authors.lastname: Hartley
authors.forename: Peter J
authors.initials: PJ
authors.lastname: McHugh
mesh_terms: D002460:Cell Line; D003432:Cross-Linking Reagents / Q000633:toxicity; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D016521:Electrophoresis, Gel, Pulsed-Field; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; D040461:Gene Components; D006801:Humans; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D043264:Phosphodiesterase I / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D015003:Yeasts
chemical_list: D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; C493741:DCLRE1B protein, human; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; C090162:PSO2 protein, S cerevisiae; D043264:Phosphodiesterase I; D045643:DNA Repair Enzymes