title: Pol32, a subunit of Saccharomyces cerevisiae DNA polymerase delta, suppresses genomic deletions and is involved in the mutagenic bypass pathway.
abstract: The Pol32 subunit of S. cerevisiae DNA polymerase (Pol) delta plays an important role in replication and mutagenesis. Here, by measuring the CAN1 forward mutation rate, we found that either POL32 or REV3 (which encodes the Pol zeta catalytic subunit) inactivation produces overlapping antimutator effects against rad mutators belonging to three epistasis groups. In contrast, the msh2Delta pol32Delta double mutant exhibits a synergistic mutator phenotype. Can(r) mutation spectrum analysis of pol32Delta strains revealed a substantial increase in the frequency of deletions and duplications (primarily deletions) of sequences flanked by short direct repeats, which appears to be RAD52 and RAD10 independent. To better understand the pol32Delta and rev3Delta antimutator effects in rad backgrounds and the pol32Delta mutator effect in a msh2Delta background, we determined Can(r) mutation spectra for rad5Delta, rad5Delta pol32Delta, rad5Delta rev3Delta, msh2Delta, msh2Delta pol32Delta, and msh2Delta rev3Delta strains. Both rad5Delta pol32Delta and rad5Delta rev3Delta mutants exhibit a reduction in frameshifts and base substitutions, attributable to antimutator effects conferred by the pol32Delta and rev3Delta mutations. In contrast, an increase in these two types of alterations is attributable to a synergistic mutator effect between the pol32Delta and msh2Delta mutations. Taken together, these observations indicate that Pol32 is important in ensuring genome stability and in mutagenesis.
authors.affiliation: UMR6061 CNRS, "Génétique et Développement," Faculté de Médecine, 35043 Rennes, France. huang@univ-rennes1.fr
authors.forename: Meng-Er
authors.initials: ME
authors.lastname: Huang
authors.forename: Anne-Gaëlle
authors.initials: AG
authors.lastname: Rio
authors.forename: Marie-Dominique
authors.initials: MD
authors.lastname: Galibert
authors.forename: Francis
authors.initials: F
authors.lastname: Galibert
mesh_terms: D002172:Canavanine / Q000494:pharmacology; D004258:DNA Polymerase III / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D025141:Drug Resistance, Fungal / Q000235:genetics; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism; D004843:Epistasis, Genetic; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D016681:Genome, Fungal; D009153:Mutagens / Q000494:pharmacology; D009154:Mutation; D051721:Rad52 DNA Repair and Recombination Protein; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D017384:Sequence Deletion; D015719:Single-Strand Specific DNA and RNA Endonucleases
chemical_list: D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D009153:Mutagens; C497197:RAD52 protein, S cerevisiae; D051721:Rad52 DNA Repair and Recombination Protein; D029701:Saccharomyces cerevisiae Proteins; D002172:Canavanine; C425929:DNA polymerase zeta; D004258:DNA Polymerase III; D004259:DNA-Directed DNA Polymerase; C092602:REV3 protein, S cerevisiae; D004720:Endonucleases; C064162:RAD10 protein, S cerevisiae; D015719:Single-Strand Specific DNA and RNA Endonucleases