| 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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| 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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