Genetics, Vol. 160, 1409-1422, April 2002, Copyright © 2002

Pol32, a Subunit of Saccharomyces cerevisiae DNA Polymerase {delta}, Suppresses Genomic Deletions and Is Involved in the Mutagenic Bypass Pathway

Meng-Er Huanga, Anne-Gaëlle Rioa, Marie-Dominique Galiberta, and Francis Galiberta
a UMR6061 CNRS, "Génétique et Développement," Faculté de Médecine, 35043 Rennes, France

Corresponding author: Meng-Er Huang, “Génétique et Développement,” Faculté de Médecine, 2 ave. du Professeur Léon Bernard, 35043 Rennes, France., huang{at}univ-rennes1.fr (E-mail)

Communicating editor: A. NICOLAS

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 msh2{Delta} pol32{Delta} double mutant exhibits a synergistic mutator phenotype. Canr mutation spectrum analysis of pol32{Delta} 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 pol32{Delta} and rev3{Delta} antimutator effects in rad backgrounds and the pol32{Delta} mutator effect in a msh2{Delta} background, we determined Canr mutation spectra for rad5{Delta}, rad5{Delta} pol32{Delta}, rad5{Delta} rev3{Delta}, msh2{Delta}, msh2{Delta} pol32{Delta}, and msh2{Delta} rev3{Delta} strains. Both rad5{Delta} pol32{Delta} and rad5{Delta} rev3{Delta} mutants exhibit a reduction in frameshifts and base substitutions, attributable to antimutator effects conferred by the pol32{Delta} and rev3{Delta} mutations. In contrast, an increase in these two types of alterations is attributable to a synergistic mutator effect between the pol32{Delta} and msh2{Delta} mutations. Taken together, these observations indicate that Pol32 is important in ensuring genome stability and in mutagenesis.




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