2009 Fiscal Year Final Research Report
Crosstalk between cell cycle regulatory mechanism and DNA repair
| Project/Area Number |
19681004
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (A)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Risk sciences of radiation/Chemicals
|
|---|
| Research Institution | Kobe University |
|---|
Principal Investigator |
NISHI Ryotaro Kobe University, 自然科学系先端融合研究環・バイオシグナル研究センター, 助教 (80446525)
|
|---|
| Project Period (FY) |
2007 – 2009
|
| Keywords | 放射線生物影響 / DNA修復 / 細胞周期 |
|---|
| Research Abstract |
Nucleotide excision repair (NER) is a versatile DNA repair mechanism that eliminates a wide variety of DNA lesions including UV-induced thymine dimers. XPC complex plays an essential role in DNA damage recognition of NER. Although centrin 2 which belongs to calmodulin super family was suggested to enhance NER by increasing DNA-binding activity of XPC, the precise mechanism of this enhancement remains to be elucidated. Biochemical studies using truncated mutant of centrin 2 indicated that C-terminal domain of centrin 2 is sufficient for enhancement of reconstituted NER and DNA-binding activity of XPC via complex formation with XPC. On the contrary, N-terminal domain interacted with UV-DDB, which is a component of E3 ligase ubiquitylating XPC according to UV irradiation. Electrophoretic mobility shift assay suggested that centrin 2 aids in formation of complex between XPC and UV-DDB on damaged-DNA. Furthermore, UV-C induced ubiquitylation of XPC was compromised in the absence of centrin 2, implying that centrin 2 might regulate ubiquitylation of XPC by interacting with two damage recognition factors via structurally independent two domains.
|
