High impact information on POL2

• Unlike sad1 mutants defective for multiple cell cycle checkpoints, pol2 mutants are defective only for the S phase checkpoint and the activation of DUN1 kinase necessary for the transcriptional response to damage [1].
• We have cloned and analyzed POL2, the gene encoding the catalytic subunit of the third nuclear DNA polymerase, DNA polymerase II [2].
• POL2 expressed a transcript of approximately 7.5 kb and contained a reading frame that encoded a protein of calculated Mr 255,649 [2].
• These results show that POL2 and RAD9 function in parallel branches for sensing and transducing the UV DNA damage signal [3].
• Finally, the viability of cells lacking Pol2 catalytic function does not require intact DNA replication or damage checkpoints [4].

Biological context of POL2

• The Schizosaccharomyces pombe homolog of DPB11, cut5, has been implicated in the DNA replication checkpoint as has the POL2 gene with which DPB11 genetically interacts [5].
• DPB11, a gene that suppresses mutations in two essential subunits of Saccharomyces cerevisiae DNA polymerase II(epsilon) encoded by POL2 and DPB2, was isolated on a multicopy plasmid [6].
• It has been proposed that C-terminal motifs of the catalytic subunit of budding yeast polymerase (pol) epsilon (POL2) couple DNA replication to the S/M checkpoint (Navas, T. A., Zheng, Z., and Elledge, S. J. (1995) Cell 80, 29-39) [7].
• Two-hybrid assays show that the POL2 subunit interacts with itself, and that the replication and checkpoint mutants are specifically defective in the interaction, suggesting (but not proving) that direct or indirect dimerization may be important for the normal functions of pol epsilon [7].
• The level of DPB3 transcript thus appears to be under the same cell cycle control as those of POL2, DPB2 and other DNA replication genes [8].

Associations of POL2 with chemical compounds

• Identification and characterization of a proliferating cell nuclear antigen consensus interaction domain on Pol2p indicates that the motif is dispensable for DNA replication but is important for methyl methanesulfonate damage-induced DNA repair [9].

Other interactions of POL2

• Repair synthesis in nuclear extracts of pol1, pol2, and pol3 temperature-sensitive mutants was normal at permissive temperatures [10].
• We previously reported that MAG1 induction was abolished in pol2 and rad53 mutants, but not in the mec1-1 mutant [11].
• The polymerase epsilon mutations, pol2-9 and pol2-18, which lead to temperature-sensitivity, and pol2-1 (insertion of URA3 at the position coding for amino acid 1134 in the POL2 gene) substantially reduced HAP mutagenesis [12].
• Here we show that the epigenetic states of the telomere gene are not stably inherited in cells either bearing a mutation in a catalytic subunit (Pol2) of replicative DNA polymerase epsilon (Pol epsilon) or lacking one of the nonessential and histone fold motif-containing subunits of Pol epsilon, Dpb3 and Dpb4 [13].
• We present evidence that pol2 mutants are defective in sister chromatid cohesion [14].

References