Disease relevance of POL32

• When POL31 and POL32 were co-expressed in Escherichia coli, a tetrameric (Pol31p.Pol32p)2 species was detected by gel filtration, indicating that the two subunits form a complex [1].

High impact information on POL32

• The pif1delta dna2delta strain remains methylmethane sulfonate sensitive and temperature sensitive; however, these phenotypes can be suppressed by further deletion of a subunit of pol delta, POL32 [2].
• The formation of MNNG-induced mutations is almost abolished in the rad30Delta pol32Delta double mutant of yeast, which lacks the RAD30 gene that encodes Poleta and the Pol32 subunit of DNA polymerase delta (Poldelta) [3].
• The amino-terminal region of Pol32 is essential for damage-induced mutagenesis [4].
• DNA polymerase delta (Pol delta) from Saccharomyces cerevisiae consists of three subunits, Pol3 (125 kDa), Pol31 (55 kDa), and Pol32 (40 kDa), present at a 1:1:1 stoichiometry in purified preparations [5].
• Previously, based on gel filtration studies of Pol delta, we suggested that the enzyme may be a dimer of catalytic cores, with dimerization mediated by the Pol32 subunit (Burgers, P. M., and Gerik, K. J. (1998) J. Biol. Chem. 273, 19756-19762) [5].

Biological context of POL32

• POL32, a subunit of the Saccharomyces cerevisiae DNA polymerase delta, defines a link between DNA replication and the mutagenic bypass repair pathway [6].
• Saccharomyces cerevisiae DNA polymerase delta (Poldelta) is a heterotrimeric enzyme consisting of Pol3 (the catalytic subunit), Pol31 and Pol32 [7].
• Taken together, these observations indicate that Pol32 is important in ensuring genome stability and in mutagenesis [8].
• All these phenotypes suggest a role for YJR043C in cell cycle progression in G2/M phase [9].

Associations of POL32 with chemical compounds

• The POL32 gene is not essential, but a deletion mutant shows cold sensitivity for growth and is sensitive to hydroxyurea and DNA damaging agents [1].
• The relative roles in vivo of Saccharomyces cerevisiae Pol eta, Pol zeta, Rev1 protein and Pol32 in the bypass and mutation induction of an abasic site, T-T (6-4) photoadduct and T-T cis-syn cyclobutane dimer [10].

Physical interactions of POL32

• The POL32 gene product binds proliferating cell nuclear antigen [1].
• Moreover, in a two-hybrid screen, we observed that Pol32 interacts with Srs2, a DNA helicase required for DNA replication and mutagenesis [6].

Other interactions of POL32

• We also found that the increase in the CAN1 spontaneous forward mutation of different rad mutators relies entirely or partially on a functional POL32 gene [6].
• In addition, lethality was observed when the POL32 deletion mutation was combined with conditional mutations in either the POL3 or POL31 gene [1].
• Simultaneous deletion of POL32 and SRS2 dramatically decreases cellular viability at 15 degrees C and greatly increases cellular sensitivity to hydroxyurea at the permissive temperature [6].
• Based on these findings, we propose that POL32 defines a link between the DNA polymerase and helicase activities, and plays a role in the mutagenic bypass repair pathway [6].
• 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 [8].

References