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] Ability of a convolutional neural network to differentiate between mouse and human cell lines and their radioresistant clones using microscopic images.2019
Author(s)
Toratani, M., Konno, M., Asai. A., Koseki, J., Kawamoto, K., Tamari, K., Li, Z., Sakai, D., Kudo, T., Satoh, T., Sato, K., Motooka, D., Okuzaki, D., Doki, Y., Mori, M., Ogawa, K., Ishii, H.
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Journal Title
Cancer Res
Volume: 72(16)
Pages: 1283-1295
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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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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