The function of the human homolog of Saccharomyces cerevisiae REV1 is required for mutagenesis induced by UV light

In Saccharomyces cerevisiae, most mutations induced by a wide range of muta gens arise during translesion replication employing the REV1 gene product a nd DNA polymerase zeta As part of an effort to investigate mammalian mutage nic mechanisms, we have identified cDNA clones of the human homologs of the yeast REV genes and examined their function in UV mutagenesis. Previously, we described the isolation of a human homolog of yeast REV3, the catalytic subunit of pol zeta, and here report the identification and sequence of a human homolog of yeast REV1. This gene was isolated by identifying an expre ssed sequence tag encoding a peptide with similarity to the C terminus of y east Rev1p, followed by sequencing of the clone and retrieval of the remain ing cDNA by 5' rapid amplification of cDNA ends. The human gene encodes an expected protein of 1,251 residues, compared with 985 residues in the yeast protein. The proteins share two amino-terminal regions of approximate to 1 00 residues with 41% and 20% identity, a region of approximate to 320 resid ues with 31% identity, and a central motif in which 11 of 13 residues are i dentical. Human cells expressing high levels of an hREV1 antisense RNA grew normally, and were not more sensitive to the cytotoxic effect of 254 nm UV radiation than cells lacking antisense RNA. However, the frequencies of C- thioguanine resistance mutants induced by UV in the cells expressing antise nse hREV1 RNA were significantly lower than in the control (P = 0.01), sugg esting that the human gene has a function similar to that of the yeast homo log.