title: The human REV1 gene codes for a DNA template-dependent dCMP transferase.
abstract: DNA is frequently damaged by various physical and chemical agents. DNA damage can lead to mutations during replication. In the yeast Saccharomyces cerevisiae, the damage-induced mutagenesis pathway requires the Rev1 protein. We have isolated a human cDNA homologous to the yeast REV1 gene. The human REV1 cDNA consists of 4255 bp and codes for a protein of 1251 amino acid residues with a calculated molecular weight of 138 248 Da. The human REV1 gene is localized between 2q11.1 and 2q11.2. We show that the human REV1 protein is a dCMP transferase that specifically inserts a dCMP residue opposite a DNA template G. In addition, the human REV1 transferase is able to efficiently and specifically insert a dCMP opposite a DNA template apurinic/apyrimidinic (AP) site or a uracil residue. These results suggest that the REV1 transferase may play a critical role during mutagenic translesion DNA synthesis bypassing a template AP site in human cells. Consistent with its role as a fundamental mutagenic protein, the REV1 gene is ubiquitously expressed in various human tissues.
authors.affiliation: Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: W
authors.initials: W
authors.lastname: Lin
authors.forename: H
authors.initials: H
authors.lastname: Xin
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: X
authors.initials: X
authors.lastname: Wu
authors.forename: F
authors.initials: F
authors.lastname: Yuan
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D019976:Cloning, Organism; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000032:analysis; D003843:Deoxycytidine Monophosphate / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009713:Nucleotidyltransferases; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D013698:Templates, Genetic; D000099270:Y-Family DNA Polymerases
chemical_list: D018076:DNA, Complementary; D003843:Deoxycytidine Monophosphate; D005656:Fungal Proteins; D009713:Nucleotidyltransferases; D029701:Saccharomyces cerevisiae Proteins; C100951:REV1 protein, S cerevisiae; D000099270:Y-Family DNA Polymerases