2005 Fiscal Year Final Research Report Summary
Origin of radiation-induced genomic instability
| Project/Area Number |
14208068
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (A)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
環境影響評価(含放射線生物学)
|
|---|
| Research Institution | Kyoto University |
|---|
Principal Investigator |
KOMATSU Kenshi Kyoto University, Radiation Biology Center, Professor, 放射線生物研究センター, 教授 (80124577)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SAKAMOTO Syuichi Kyoto University, Radiation Biology Center, Assistant Professor, 放射線生物研究センター, 助手 (60346070)
KOBAYASHI Junya Kyoto University, Radiation Biology Center, Assistant Professor, 放射線生物研究センター, 助手 (30301302)
|
|---|
| Project Period (FY) |
2002 – 2005
|
| Keywords | Homologous recombination / Genome stability / NBS1 / MRE11 / ATM / WRN / Nijmegen breakage syndrome / Ataxia-telangiectasia |
|---|
| Research Abstract |
NBS1 is a responsible protein for recessive hereditary disease Nijmegen breakage syndrome, which is characterized by high sensitivity to ionizing radiation, chromosomal instability and predisposition to tumor. We demonstrated here that NBS1 regulates homologous recombination repair and the patients with defect in homologous recombination can survive, while it causes genomic instability and tumorigenesis. Present results also showed that NBS1 recruits MRE11 nuclease to sites of double strand breaks through interaction with histon H2AX. In addition to these interactions, NBS1 also binds to WRN, a protein for accelerated aging disease Werner syndrome, and FANC, a protein for recessive hereditary disease Fancony anemia, which is characterized by high sensitivity to inter-crosslinked DNA damage. Although their role in response to double strand breaks remains elusive, this repair network could contribute to genome stability after generation of DNA damage. On the basis of phenotypic resembles, Nijmegen breakage syndrome is categolized to Ataxia telangiectasia (A-T), which is mutated in ATM protein, and A-T like disorder, which is defective in MRE11. Our results also showed that NBS1 is associated with ATM and MRE11for cell cycle checkpoint but not for DNA repair via homologous recombination. Taken together, these results could shed light on a crossroad between checkpoint and DNA repair, whereas they must associated to maintain genome stability after exposure to ionizing radiation.
|
