Abstract
Mutagenesis is a cellular response to the DNA damage. This biological function is essential for the maintenance of chromosomal integrity as well as the DNA repair function. It has been suggested that functions of the REV1, REV3, REV7 and POL32 genes are required for error-prone post-replication repair, essential for induction of mutations and prevention of cell death caused by ionizing radiation. Rev1 protein is the deoxycytidyl transferase and a member of the Y-family DNA polymease. The activity is capable of extending a primer terminus by insertion of dCMP opposite a variety of damaged bases. REV3 and REV7 encode another error-prone DNA polymerase, polζ. Pol32 is one of the subunits of a replicative DNA polymerase, polδ, and has a function interacting with PCNA. These genetic data suggest that those proteins form specialized machinery for translesion DNA synthesis. To elucidate molecular mechanisms of the induced mutagenesis in humans, the human proteins have been purified from overproduced Escherichia coli cells. We have demonstrated that the human REV1 protein is the deoxycytidyl transferase and forms a stable heterodimer with REV7. Recently, it has been found that the REV1 interacts with all of the Y-family DNA polymerases, polη, polι and polκ, suggesting the central role of REV1 protein in the translesion DNA synthesis. In this symposium, we present the biochemical property of the REV1 protein and discuss the molecular role of this protein in the translesion DNA replication.
