Disease relevance of REV1

• Furthermore, Rev1p is needed only for non-slipped TLS; slipped TLS remains efficient in its absence, revealing a previously uncharacterized Rev1p activity similar to Escherichia coli UmuDC function [1].

High impact information on REV1

• 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 [2].
• REV1 protein, a eukaryotic member of the Y family of DNA polymerases, is involved in the tolerance of DNA damage by translesion DNA synthesis [3].
• In vivo studies in both chicken DT40 cells and yeast directly support the requirement of the BRCT domain of REV1 for cell survival and DNA damage-induced mutagenesis [3].
• To examine the role of Rev1 in vertebrate mutagenesis and the DNA damage response, we disrupted the gene in DT40 cells [4].
• Furthermore, ultraviolet exposure results in marked chromosome breakage, suggesting that replication gaps created in the absence of Rev1 cannot be efficiently repaired by recombination [4].

Biological context of REV1

• Furthermore, REV1-/- cells as well as triple mutants showed a decreased level of immunoglobulin gene conversion, suggesting participation of Rev1 in a recombination-based pathway [5].
• Human homologues of the yeast REV1 and REV3 have been identified and, based on the phenotype of cells producing antisense RNA to one or other of these genes, their products appear also to be employed in translation replication and spontaneous mutagenesis [6].
• The human homologs of S. cerevisiae REV1, REV3, and REV7 were identified, and it is revealed that the human REV proteins have similar functions to their yeast counterparts, however, a large part of the mechanisms of mutagenesis employing REV proteins are still unclear [7].
• Epistatic participation of REV1 and REV3 in the formation of UV-induced frameshift mutations in cell cycle-arrested yeast cells [8].
• REV1 is central to the DNA damage response of eukaryotes through an as yet poorly understood role in translesion synthesis [9].

Anatomical context of REV1

• These C-terminal domains of REV1 are necessary, although not sufficient, for effective tolerance of DNA damage in the avian cell line DT40, while the BRCT domain and transferase activity are not directly required [9].
• Here, we disrupted Rev1, Rev3, and Rev7 in the chicken B-lymphocyte line DT40 [5].
• This is the first report demonstrating that the DNA polymerase zeta and Rev1 proteins function in the mitochondria [10].

Associations of REV1 with chemical compounds

• 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 [11].
• Deletion of REV1 decreased the transformation efficiency and the incorporation of cytosine nearly to a background level [12].
• To test this idea, we examined whether Rev1 could incorporate a C opposite the gamma-hydroxy-1,N(2)-propano-2'deoxyguanosine DNA minor-groove adduct, which is formed from the reaction of acrolein with the N(2) of guanine [13].
• We show that Rev1 specifically inserts a C residue opposite template G, and it is approximately 25-, 40-, and 400-fold less efficient at inserting a C residue opposite an abasic site, an O(6)-methylguanine, and an 8-oxoguanine lesion, respectively [14].
• We have analyzed the role of Rev1 in translesion synthesis of an acetylaminofluorene (AAF)-dG DNA adduct [15].

Physical interactions of REV1

• Here, we provide evidence for the physical association of Rev1 with Polzeta and show that this binding is mediated through the C terminus of Rev1 and the polymerase domain of Rev3 [16].
• Importantly, the polymerase-associated domain (PAD) of Rev1 mediates its binding to Rev7 [17].

Regulatory relationships of REV1

• Importantly, a rev1 mutant that lacks the C-terminal 72 residues which inactivate interaction with Rev3 exhibits the same high degree of UV sensitivity and defectiveness in UV-induced mutagenesis as that conferred by the rev1Delta mutation [16].

Other interactions of REV1

• Employing the same two conditions, we now examined the effect of deletions of the genes coding for polymerase eta (Pol eta) (RAD30) and Rev1p (REV1) [8].
• The availability of PCNA monoubiquitylated on all of its three monomers has enabled us to examine the effects of this PCNA modification on DNA synthesis by Pols delta, eta, zeta, and Rev1 [18].
• Ultraviolet-induced reversion of cyc1 alleles in radiation-sensitive strains of yeast. I. rev1 Mutant strains [19].
• To better understand the nature of these mechanisms, we determined the DNA sequence changes of 232 independent, spontaneous frameshift mutations in the HIS4 gene of REV1 and rev1-1 strains of Saccharomyces cerevisiae [20].
• This genetic dependency may suggest a role for MEC1 in spontaneous mutagenesis events, which require a functional REV1 gene [21].

References