| Research Abstract |
Human DNA polymerase η is the XPV gene product which is responsible for a cancer-prone genetic disease, keroderma pigmentosum variant. We are interested in DNA polymerase η which we have identified in 1,999. DNA polymerase η is a novel type of DNA polymerase and catalyzes translesion snthesis across cyclobutane pyrimidine dimers, the major DNA lesions induced by UV-irradiation, in an accurate manner. Since classical replicative DNA polymerases α, δ, and ε can not catalyze TLS past the lesions, DNA polyrnerase η plays an important role in the replication of DNA containing lesions. Little is known concerning the regulatory mechanisms of DNA polymerase η. Here we investigated DNA polymerase η-interacting proteins.
Using yeast two-hybrid systems, pull-down analyses with recombinant proteins, and co-expression experiments in eukaryotic cells, we found that DNA polymerase η interacts with Rev1 and PCNA. Rev1 is a deoxycytidiltransferase involved in the error-prone translesion synthesis. PCNA is a sliding clamp of replicative NA polymerases δ and ε. So, these interactions may contribute to the DNA polymerase switching and/or DNA polymerase selection at various lesion sites. Based on the results, mechanisms for translesion synthesis in human cells will be clarified in near future.
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