Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.7 (DNA polymerase)
17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We measured the relative steady-state levels of the mRNA transcribed from the Saccharomyces cerevisiae REV3 gene in cells at different stages of the mitotic and meiotic cycles, and after UV irradiation. This gene is thought to encode a DNA polymerase concerned only with a specific recovery function, the replication on mutagen-damaged templates that produces damaged-induced mutations. In keeping with this proposed function, the REV3 gene showed no evidence of the periodic transcription at the G1/S boundary of the mitotic and meiotic cycle that occurs with genes encoding replication enzymes. However, levels of REV3 mRNA were much increased in late meiotic cells, like those of transcripts of some other DNA repair-related genes. Steady-state levels of REV3 transcript were increased only slightly in response to UV irradiation.
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PMID:The REV3 gene of Saccharomyces cerevisiae is transcriptionally regulated more like a repair gene than one encoding a DNA polymerase. 149 46

We have cloned the REV3 gene of Saccharomyces cerevisiae by complementation of the rev3 defect in UV-induced mutagenesis. The nucleotide sequence of this gene encodes a predicted protein of Mr 172,956 showing significant sequence similarity to Epstein-Barr virus DNA polymerase and to other members of a class of DNA polymerases including human DNA polymerase alpha and yeast DNA polymerase I. REV3 protein shows less sequence identity, and presumably a more distant evolutionary relationship, to the latter two enzymes than they do to each other. Haploids carrying a complete deletion of REV3 are viable. We suggest that induced mutagenesis in S. cerevisiae depends on a specialized DNA polymerase that is not required for other replicative processes. REV3 is located 2.8 centimorgans from CDC60, on chromosome XVI.
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PMID:REV3, a Saccharomyces cerevisiae gene whose function is required for induced mutagenesis, is predicted to encode a nonessential DNA polymerase. 267 86

The Saccharomyces cerevisiae rad6, rad18, and rad52 mutants exhibit DNA repair deficiencies and distinct mutator phenotypes. DNA replication past unrepaired spontaneous damage might contribute to the specificities of these mutators. Because REV3 is thought to encode a DNA polymerase that specializes in translesion synthesis, we determined the REV3 dependence of the rad mutator specificities. Spontaneous mutagenesis at a plasmid-borne SUP4-o locus was examined in isogenic strains having combinations of normal or mutant REV3 and RAD6, RAD18, or RAD52 alleles. For the rad6 and rad18 mutators, the mutation rate increase relied largely, but not exclusively, on REV3 whereas the rad52 mutator was entirely REV3 dependent. The influence of REV3 on the specificity of the rad6 mutator differed markedly depending on the mutational class examined. However, the requirement of rev3 for the production of G.C-->T.A transversions by the rad18 mutator, which induces only these substitutions, was similar to that for rad6-mediated G.C-->T.A transversion. This supports a role for the Rad6-Rad18 protein complex in the control of spontaneous mutagenesis. The available data imply that the putative Rev3 polymerase can process a variety of spontaneous DNA lesions that normally are substrates for error-free repair.
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PMID:Specificities of the Saccharomyces cerevisiae rad6, rad18, and rad52 mutators exhibit different degrees of dependence on the REV3 gene product, a putative nonessential DNA polymerase. 749 27

The yeast REV3 gene has been predicted to encode a DNA polymerase specializing in translesion synthesis. This polymerase likely participates in spontaneous mutagenesis, as rev3 mutants have an antimutator phenotype. Translesion synthesis also may be necessary for the mutator caused by a RAD1 (nucleotide excision repair) deletion (rad1 delta). To further examine the role of REV3 in spontaneous mutagenesis, we characterized SUP4-o mutations that arose spontaneously in strains having combinations of normal or mutant REV3 and RAD1 alleles. The largest fraction of the rev3 delta-dependent mutation rate decrease was observed for single base-pair substitutions and deletions, although the rates of all mutational classes detected in the RAD1 background were reduced by at least 30%. Interestingly, inactivation of REV3 was associated with a doubling of the number of sites at which the retrotransposon Ty inserted. rev3 delta also greatly diminished the magnitude of the rad1 delta mutator, but not to the rev3 delta antimutator level, implicating REV3-dependent and independent processes in the rad1 delta mutator effect. However, the specificity of the rev3 delta antimutator suggested that the same REV3-dependent processes gave rise to the majority of spontaneous mutations in the RAD1 and rad1 delta strains.
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PMID:Specificity of the yeast rev3 delta antimutator and REV3 dependency of the mutator resulting from a defect (rad1 delta) in nucleotide excision repair. 808 9

Base excision repair is an important mechanism for correcting DNA damage produced by many physical and chemical agents. We have examined the effects of the REV3 gene and the DNA polymerase genes POL1, POL2, and POL3 of Saccharomyces cerevisiae on DNA repair synthesis is nuclear extracts. Deletional inactivation of REV3 did not affect repair synthesis in the base excision repair pathway. Repair synthesis in nuclear extracts of pol1, pol2, and pol3 temperature-sensitive mutants was normal at permissive temperatures. However, repair synthesis in pol2 nuclear extracts was defective at the restrictive temperature of 37 degrees C and could be complemented by the addition of purified yeast DNA polymerase epsilon. Repair synthesis in pol1 nuclear extracts was proficient at the restrictive temperature unless DNA polymerase alpha was inactivated prior to the initiation of DNA repair. Thermal inactivation of DNA polymerase delta in pol3 nuclear extracts enhanced DNA repair synthesis approximately 2-fold, an effect which could be specifically reversed by the addition of purified yeast DNA polymerase delta to the extract. These results demonstrate that DNA repair synthesis in the yeast base excision repair pathway is catalyzed by DNA polymerase epsilon but is apparently modulated by the presence of DNA polymerases alpha and delta.
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PMID:DNA repair synthesis during base excision repair in vitro is catalyzed by DNA polymerase epsilon and is influenced by DNA polymerases alpha and delta in Saccharomyces cerevisiae. 842 75

The REV3 and REV7 genes of the yeast Saccharomyces cerevisiae are required for DNA damage-induced mutagenesis. The Rev3 and Rev7 proteins were shown to form a complex with DNA polymerase activity. This polymerase replicated past a thymine-thymine cis-syn cyclobutane dimer, a lesion that normally severely inhibits replication, with an efficiency of approximately 10 percent. In contrast, bypass replication efficiency with yeast DNA polymerase alpha was no more than 1 percent. The Rev3-Rev7 complex is the sixth eukaryotic DNA polymerase to be described, and is therefore called DNA polymerase zeta.
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PMID:Thymine-thymine dimer bypass by yeast DNA polymerase zeta. 865 38

Genetic control of mutagenesis by the base analog 6-N-hydroxylaminopurine (HAP) was studied in a set of isogenic yeast strains carrying null or point mutations in DNA repair and replication genes. Null alleles of the PMS1, RAD6, REV3 and RAD52 genes did not affect HAP mutagenesis. Defects in 3'- > 5' exonucleases associated with DNA polymerases epsilon and delta led to 2- to 3-fold increases in HAP-induced forward Can(r) mutant frequency. A similar increase was observed for FOAr mutants but only in the strain with a defective exonuclease of the polymerase epsilon (mutation pol2-4). 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. The polymerase delta mutation, cdc2-2, slightly reduced HAP mutagenesis. Enhanced proofreading was not the cause of the antimutator effect in the pol2-18 bearing strain, inasmuch as antimutator effect was observed in the pol2-4,18 mutant strain lacking proofreading. From the data obtained, we conclude that both DNA polymerase epsilon and delta participate in mutation generation by HAP.
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PMID:Base analog 6-N-hydroxylaminopurine mutagenesis in the yeast Saccharomyces cerevisiae is controlled by replicative DNA polymerases. 870 Jan 80

Mutagenesis induced by DNA damage in Saccharomyces cerevisiae requires the products of the REV1, REV3 and REV7 genes. The Rev3 and Rev7 proteins are subunits of DNA polymerase-zeta (Pol-zeta), an enzyme whose sole function appears to be translesion synthesis. Rev1 protein has weak homology with UmuC protein which facilitates translesion synthesis in Escherichia coli by an unknown mechanism. We show here that Rev1 protein has a deoxycytidyl transferase activity which transfers a dCMP residue from dCTP to the 3' end of a DNA primer in a template-dependent reaction. Efficient transfer occurred opposite a template abasic site, but approximately 20% transfer also occurred opposite a template guanine and approximately 10% opposite adenine or uracil; < or = 1% was seen opposite thymine or cytosine. Insertion of cytosine opposite an abasic site produced a terminus that was extended efficiently by Pol-zeta, but not by yeast Pol-alpha.
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PMID:Deoxycytidyl transferase activity of yeast REV1 protein. 875 46

DNA damage induced mutations arising during the course of translesion replication are likely to be an important contributory cause in the development of many cancers. In budding yeast, Saccharomyces cerevisiae, a good model system with which to investigate this process, mutagenesis is associated with the RAD6 repair pathway and depends on the functions of the REV1, REV3 and REV7 genes. The Rev3 and Rev7 proteins are subunits of a new type of DNA polymerase, called DNA polymerase zeta, that appears to carry out translesion replication, but no other repair, recombination or replication function. Pol zeta replicates past a T-T cyclobutane dimer with a higher efficiency than yeast pol alpha, is less prone than this enzyme to insert an incorrect nucleotide and is more efficient at elongating from a mismatched terminus. Rev1 protein is a terminal nucleotidyl transferase that inserts dCMP opposite template G, A and abasic sites. Types of mutations induced during translesion replication appear to depend largely on lesion structure, but the frequency and accuracy of bypass also depend on replication conditions. Inhibition of the activity or expression of pol zeta may be clinically useful for patients undergoing cancer therapy or for those with a familial predisposition to cancer.
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PMID:DNA polymerase zeta and the control of DNA damage induced mutagenesis in eukaryotes. 897 26

The ability of four yeast DNA polymerase mutant strains to carry out the repair of DNA treated with MMS was studied. Mutation in DNA polymerase Rev3, as well as the already known mutation in the catalytic subunit of DNA polymerase delta, were both found to lead to the accumulation of single-strand breaks, which indicates defective repair. A double-mutant strain carrying mutations in DNA polymerase delta and a deletion in the REV3 gene had a complete repair defect, both at permissive (23 degrees C) and restrictive (38 degrees C) temperatures, which was not observed in other pairwise combinations of tested polymerase mutants. Other polymerases are not involved in the repair of exogenous DNA methylation damage, since neither mutation in the DNA polymerase epsilon, nor deletion in the DNA polymerase IV (beta70) gene, caused defective repair. The data obtained suggest that DNA polymerases delta and Rev3p are both necessary to perform repair synthesis in the base-excision repair of methylation damage. The results are discussed in the light of current concepts on the role of DNA polymerase Rev3 in mutagenesis.
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PMID:Involvement of the RE V3 gene in the methylated base-excision repair system. Co-operation of two DNA polymerases, delta and Rev3p, in the repair of MMS-induced lesions in the DNA of Saccharomyces cerevisiae. 910 36


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