Suppression of DNA-damage dependent total chromatid premature separation by p53-binding protein 1
| Project/Area Number |
15590255
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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 |
General medical chemistry
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| Research Institution | KANAZAWA MEDICAL UNIVERSITY |
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Principal Investigator |
IWABUCHI Kuniyoshi Kanazawa Medical University, Department of Medicine, Associate professor, 医学部, 助教授 (10232696)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2003: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | p53 / 53BP1 / sister chromatid / DNA damage / Cytoplasmic dynein / ATM / DNA repair / 分子生物学 / 細胞周期 |
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| Research Abstract |
Upon DNA damage, p53-binding protein 1 (53BP1) relocalizes to discrete nuclear foci, suggesting its role in DNA damage responses. We have identified that a colon cancer cell line SW48 is deficient in 53BP1 expression and established a cell line, SW48dox53BP1, which expresses 53BP1 in a doxycycline-repressible manner. When 53BP1 non-expressing cells were irradiated with X-ray, they showed total premature chromatid separation (PCS), a phenotype that shows sister chromatid separation even though cells are in the metaphase. The PCS phenotype was not observed in 53BP1 expressing cells, suggesting that 53BP1 regulates sister chromatid separation in cells irradiated with X-ray. 53BP1 specifically stimulated end-joining by DNA ligase IV/Xrcc4, suggesting that 53BP1 directly participates in the non-homologous end-joining (NHEJ) repair of DNA double-strand breaks (DSBs). We further investigated 53BP1 functions in DNA DSB repair using 53BP1-knockout chicken DT40 cells, and found that 53BP1 is involved in an alternative DSB repair pathway that, unlike the classical NHEJ, is resistant to wortmannin and functions preferentially in the G1 phase of the cell cycle.
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Report
(3 results)
Research Products
(8 results)
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[Journal Article] Potential role for 53BP1 in DNA-end joining repair through direct interaction with DNA.2003
Author(s)
Iwabuchi K, Basu, B.P, Kysela B, Kurihara T, Shibata T, Guan D, Cao Y, Hamada T, Imamura K, Jeggo P A, Date T, Doherty A J.
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Journal Title
J.Biol.Chem. 278(38)
Pages: 36478-36495
Description
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