DNA damage can cause mutations which in turn may lead to carcinogenesis. In the yeast Saccharomyces cerevisiae, DNA damage-induced mutagenesis pathway requires the REV3 gene. It encodes the catalytic subunit of DNA polymerase ζ that specifically functions in translesion DNA synthesis. We have cloned a cDNA of the human homologue of REV3 (hREV3), which consists of 10,716 bp and codes for a protein of 3130 amino acid residues (352,737 Da). Its C-terminal 755 amino acids show extensive homology with the yeast protein at the C-terminus: 43% identity and 74% similarity. This region contains the six highly conserved DNA polymerase motifs. Furthermore, we have identified four sequence motifs in the N-terminal region outside the polymerase domain that are conserved in DNA polymerase δ from various sources. Three of which are present in DNA polymerase ζ encoded by human, yeast, and plant REV3 genes, indicating that this protein is a member of the DNA polymerase δ family. DNA polymerases δ and ζ are structurally distinguished by the presence of a specific δIV motif in the former and motifs ζI and ζII in the latter, respectively. Human DNA polymerase ζ is ubiquitously expressed in various tissues, consistent with the notion that the hREV3 pathway may be a fundamental mechanism of damage-induced mutagenesis in humans. Copyright (C) 1999 Elsevier Science B.V.
|Number of pages||10|
|Journal||Mutation Research - DNA Repair|
|State||Published - Mar 10 1999|
Bibliographical noteFunding Information:
We thank Deepak Rajpal for constructing plasmid pUC19M1. These studies were supported by a grant from UKMC Research Fund of the University of Kentucky, a THRI grant from Tobacco and Health Research Institute of the University of Kentucky, and a New Investigator Award in Toxicology from Burroughs Wellcome Fund.
Copyright 2007 Elsevier B.V., All rights reserved.
- DNA damage
- DNA polymerase
ASJC Scopus subject areas
- Molecular Biology