ENOMOTO Takemi Tohoku University, Graduate School of Pharmaceutical Science, Professor, 薬学研究科, 教授 (80107383)
OHMORI Haruo Kyoto University, Institute for Virus, Associate Professor, ウィルス研究所, 助教授 (10127061)
|Budget Amount *help
¥87,400,000 (Direct Cost: ¥87,400,000)
Fiscal Year 2005: ¥17,800,000 (Direct Cost: ¥17,800,000)
Fiscal Year 2004: ¥17,600,000 (Direct Cost: ¥17,600,000)
Fiscal Year 2003: ¥17,000,000 (Direct Cost: ¥17,000,000)
Fiscal Year 2002: ¥17,000,000 (Direct Cost: ¥17,000,000)
Fiscal Year 2001: ¥18,000,000 (Direct Cost: ¥18,000,000)
To understand the comprehensive picture of genome maintenance in animal cells, we analyzed mutant cell line deficient for homologous recombination (HR), translesion synthesis (TLS), and RecQ helicases. HR plays a critical role in the maintenance of the genome, as illustrated by the spontaneous chromosomal aberrations in Arad51, Arad51B/C/D, Axrcc2/3. On the other hand, TLS, which includes RAD18, and POLh, POLz, POLK, POLQ, polymerases, plays a back up role in maintenance genome. Both HR and TLS deficiency causes synthetic lethality to cells, as illustrated by the inviability of rad18/rad54 or polz/rad54. In addition, RAD18, POLK and POLZ play a critical role in the repair of DNA lesions induced by hormone or some kind of drugs. RecQ helicase including WRN and BLM helicases co-localized with replication fork and contributes to chromosomal stability. We identified the proteins interact with these helicases and investigate the genetic interaction.
To return our basic results to public benefit, we assembled a panel consisting of a series of DNA repair DT40 mutants. The panel of mutant cell is useful in defecting the genotoxicity of the chemicals and drugs. Furthermore, it is also helpful to discover the cellular pathways involved in the repair of genotoxin, such as chemotherapeutic agents. By using the panel, we revealed the genotoxicity of nitric oxidase (NO), Tamoxifen (preventive agent for breast cancer) and identified the repair pathway of chemotherapeutic cross-linking agent cisplatine.