Functional analysis of BRCA1 as the molecular basis of breast cancer therapy
| Project/Area Number |
26290042
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | St. Marianna University School of Medicine |
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Principal Investigator |
OHTA Tomohiko 聖マリアンナ医科大学, 医学研究科, 教授 (60233136)
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| Co-Investigator(Kenkyū-buntansha) |
朴 成和 国立研究開発法人国立がん研究センター, 中央病院, 科長 (50505948)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2016: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
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| Keywords | 乳癌 / 治療 / BRCA1 / BARD1 / DNA損傷 |
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| Outline of Final Research Achievements |
In this study, we found that BARD1 interacts with Lys9-dimethylated histone H3 (H3K9me2) after DNA damage in an ATM-dependent but RNF168-independent manner. This interaction is mediated by HP1-gamma. A conserved HP1-binding motif in the BARD1 BRCT domain directly interacts with the chromoshadow domain of HP1 in vitro; mutations in this motif disrupt the retention of BRCA1/BARD1 at DNA double-strand break (DSB) sites. The inhibition of BARD1-HP1 interaction also inhibits accumulation of CtIP, FANCJ and RAD51 at DSB sites, suppressed damage-induced sister chromatid exchange, and allow ectopic accumulation of RIF1, an effector of non-homologous end joining, at the damaged loci in S-phase. The results indicate that the BARD1-HP1 interaction is critical to mediate homologous recombination repair of DSB.
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Report
(4 results)
Research Products
(35 results)
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[Journal Article] Liganded ERαstimulates the E3 ubiquitin ligase activity of UBE3C to facilitate cell proliferation2015
Author(s)
Okada, M., Ohtake, F., Nishikawa, H., Wu, W., Saeki, Y., Tanaka, K., and Ohta, T.
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Journal Title
Mol Endocrinol.
Volume: 29
Pages: 1646-1657
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] NF-kB signaling mediates acquired resistance after PARP inhibition.2015
Author(s)
Nakagawa Y, Sedukhina AS, Okamoto N, Nagasawa S, Suzuki N, Ohta T, Hattori H, Roche-Molina M, Narváez AJ, Jeyasekharan AD, Bernal JA, Sato K.
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Journal Title
Oncotarget.
Volume: 6
Pages: 3825-3539
Related Report
Peer Reviewed
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[Journal Article] LSD1 Overexpression Is Associated with Poor Prognosis in Basal-Like Breast Cancer, and Sensitivity to PARP Inhibition.2015
Author(s)
Nagasawa S, Sedukhina AS, Nakagawa Y, Maeda I, Kubota M, Ohnuma S, Tsugawa K, Ohta T, Roche-Molina M, Bernal JA, Narváez AJ, Jeyasekharan AD, Sato K.
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Journal Title
DOI
Related Report
Peer Reviewed
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[Journal Article] Ubiquitn acetylation inhibits polyubiquitin chain elongation2015
Author(s)
Ohtake, F., Saeki, Y., Sakamoto, K., Ohtake, K., Nishikawa, H., Tsuchiya, H., Ohta, T., Tanaka, K., and Kanno, J.
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Journal Title
EMBO Rep.
Volume: 16
Pages: 192-201
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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