2015 Fiscal Year Final Research Report
Development of new radiosensitizer based on the molecular mechanism of the recognition and repair of DNA double-strand break
| Project/Area Number |
24390290
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Partial Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Radiation science
|
|---|
| Research Institution | Tokyo Institute of Technology |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2012-04-01 – 2016-03-31
|
| Keywords | 放射線 / 癌治療 / DNA二重鎖切断 / DNA修復 / DNA依存性プロテインキナーゼ / XRCC4 / DNA ligase IV / タンパク質リン酸化 |
|---|
| Outline of Final Research Achievements |
This study aimed to clarify the regulatory mechanisms of protein-protein interaction mediated through DNA damage-induced phosphorylation of XRCC4 by DNA-PK and to explore their potential in application to the development of new radiosensitizer. The main achievements of this study include finding the importance of XRCC4 extremely C-terminal (XECT) region, which is highly conserved among vertebrates, the mechanisms of the nuclear localization and chromatin binding of XRCC4/LIG4 complex and the detection of XRCC4 S320 phosphorylation by DNA-PK in living cells. Based on these results, we tested possible radiosensitizing effects of XRCC4 phosphorylation-mimicking synthetic peptide, but the expected effects were not obtained, requiring further studies to optimize peptide sequence and the protocol of introduction into cells.
|
| Free Research Field |
放射線生物学・医学
|
