The human REV1 gene codes for a DNA template-dependent dCMP transferase

DNA is frequently damaged by various physical and chemical agents. DNA dama ge can lead to mutations during replication. In the yeast Saccharomyces cer evisiae, 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 re sidues with a calculated molecular weight of 138 248 Da. The human REV1 gen e is localized between 2q11.1 and 2q11.2. We show that the human REV1 prote in is a dCMP transferase that specifically inserts a dCMP residue opposite a DNA template G. In addition, the human REV1 transferase is able to effici ently and specifically insert a dCMP opposite a DNA template apurinic/apyri midinic (AP) site or a uracil residue. These results suggest that the REV1 transferase may play a critical role during mutagenic translesion DNA synth esis 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.