Abstract
When DNA is damaged by UV irradiation or alkylating reagents, various DNA repair system recognize the damages and work to repair. However, the efficiency of repair is not so high that remaining DNA damages causes hindrance to DNA replication. There is a mechanism to maintain replication of DNA strand harboring DNA damages to ensure cell growth under stressful conditions, so called DNA damage tolerance. Rad18 is a key molecule of the mechanism. Rad18 directs mono-ubiquitination of PCNA to regulate cellular localization of translesion polymerase. To investigate role of Rad18 on tumor prevention, we prepared Rad18 knockout mouse and examined spontaneous tumor frequency. The mice at 1.5 year-old showed about 2 times higher spontaneous tumor than those of wild-type mice. The tumor spectrum for tumor species and organs were totally different compared with wild-type mice. Next, we compared Rad18 expression level of transformed human cell lines and cell lines derived from tumor patients with those of primary human cells. The Rad18 expression levels of the cell lines were greatly elevated compared to primary cells. We are now examining Rad18 expression level in tumor patient tissues.
