2007 Fiscal Year Final Research Report Summary
c-Abl regulates Rad51 chromatin association
| Project/Area Number |
18590286
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Kanazawa University |
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Principal Investigator |
YAMAMOT Kenichi Kanazawa University, Cancer Research Institute, Institute (60115285)
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| Project Period (FY) |
2006 – 2007
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| Keywords | DNA Repair / Homoloaous Recombination / Rad51 / c-Abl / Tyrosine Phosohorvlation / Self-Association / Focus Formation / Glivec |
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| Research Abstract |
c-Abl tyrosine kinase is activated by DNA damage, such as ionizing radiation (IR), in an ATM-dependent manner, and plays important roles in growth arrest and cell death. c-Abl has also been shown to be involved in DNA repair through the phosphorylation of Rad51, a key molecule in homologous recombination repair (HRR). However, it is unclear how c-Abl mechanistically regulates Rad51 functions. In the present study, we show that c-Abl associates and is activated in the chromatin in kinase activity dependent manners. By using self-association defective Rad51 mutants, we further show that c-Abl phosphorylates and stabilizes Rad51 chromatin association in a Tyr-31 5-dependent manner. However, c-Abl cannot restore the defect of the self-association defective mutants in IR-induced nuclear focus formation, suggesting that c-Abl functions the early step of Rad51 chromatin assembly, before self-association-dependent Rad51 nucleoprotein filament formation at DNA damage sites.
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Research Products
(40 results)
