| Budget Amount *help |
¥44,070,000 (Direct Cost: ¥33,900,000、Indirect Cost: ¥10,170,000)
Fiscal Year 2011: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
Fiscal Year 2010: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
Fiscal Year 2009: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
Fiscal Year 2008: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
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| Research Abstract |
This study has been aimed to elucidate novel molecular mechanisms involved in spatio-temporal regulation of mammalian nucleotide excision repair(NER), focusing on post-translational modifications(ubiquitylation and sumoylation) of the damage recognition proteins, XPC and DDB2. Concerning the UV-induced reversible ubiquitylation of XPC, knockdown of the identified deubiquitylation factor was found to result in accumulation of ubiquitylated XPC, which significantly compromised recruitment of XPC to damaged DNA sites. We also succeeded in reconstitution of in vitro sumoylation of XPC and identification of the modification sites. The cells stably expressing the non-sumoylated mutant XPC exhibited retardation of NER and impaired induction of XPC ubiquitylation after UV irradiation, possibly because the functional interaction between XPC and DDB2 may be mediated by SUMO. Finally, target sites for DDB2 self-ubiquitylation by the CRL4^<DDB2> ubiquitin ligase were identified, suggesting the possibility that DDB2 ubiquitylation may have distinct roles, protein degradation and dissociation from damaged DNA, depending on the modification sites.
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