Abstract
The genomes of all living cells are continuously under attack by a variety of genotoxic agents. Translesion DNA synthesis (TLS) is one of the pathways to bypass DNA lesions with low fidelity of nucleotide insertion. TLS is believed to be the major source of DNA damage-induced point mutations and to have a close association with cancer. Many of TLS enzymes belong to the Y-family DNA polymerase, which can replicate various DNA template lesions. Member of Y-family in higher eukaryotic cells include polη, ι, κ, Rev1. Rev1 is highly conserved from bacteria to vertebrate and assumed to be an essential regulator of TLS events. Disruption of Rev1 is sensitive to a wide range of DNA-damaging agents, such as UV light, hydrogen peroxide, cisplatin, and X-ray.
To determine the role of Rev1 on radioresponse in a mouse model, Rev1 transgenic mice carrying murine Rev1 cDNA under the metallothionein promoter were constructed. We quantified radiation-induced somatic mutant frequencies by measuring T-cell receptor (TCR) in Rev1 Tg mice both before and after exposure to irradiation. TCR mutation assay is a sensitive indicator of exposure to ionizing radiation. We also measured the number of micronucleated reticulocytes in peripheral blood of Rev1 Tg mice in order to evaluate the radiation sensitivity. Both assays indicated the different radioresponse in Rev1 Tg mice compared with wild-type mice, which is supposed to the involvement of Rev1 on radioresponse.
