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.
Original language | English |
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Pages (from-to) | 4468-4475 |
Number of pages | 8 |
Journal | Nucleic Acids Research |
Volume | 27 |
Issue number | 22 |
DOIs | |
State | Published - Nov 15 1999 |
Bibliographical note
Funding 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.
Funding
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.
Funders | Funder number |
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Tobacco and Health Research Institute of the University of Kentucky | |
Burroughs Wellcome Fund |
ASJC Scopus subject areas
- Genetics