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.
|Number of pages
|Nucleic Acids Research
|Published - Nov 15 1999
Bibliographical noteFunding Information:
We thank Richard Cunningham and Christopher Lawrence for providing us with purified E.coli endonuclease III and the yeast strain CL1265-7C, respectively. We thank Deepak Rajpal for constructing plasmid pUC19M1. We thank Deepak Rajpal and Elizabeth Lin for critical review of this manuscript. These studies were supported by a THRI grant from the Tobacco and Health Research Institute of the University of Kentucky and a New Investigator Award in Toxicology from the Burroughs Wellcome Fund.
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