DNA double-strand break repair regulated by nuclear bodies
| Project/Area Number |
16H05888
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Risk sciences of radiation and chemicals
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| Research Institution | Ritsumeikan University |
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Principal Investigator |
Nishi Ryotaro 立命館大学, 生命科学部, 助教 (80446525)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥23,400,000 (Direct Cost: ¥18,000,000、Indirect Cost: ¥5,400,000)
Fiscal Year 2019: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2016: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
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| Keywords | DNA修復 / 相同組換え修復 / 核内構造体 / Nuclear speckles / ユビキチン化 / 脱ユビキチン化 / R-loop / DNA二重鎖切断 / nuclear speckles / DSB修復 / DSB応答 / 放射線 / ゲノム |
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| Outline of Final Research Achievements |
The integrity of genomic DNA that is challenged by various endogenous and exogenous sources is maintained by DNA repair mechanisms that remove and repair a wide variety of DNA damages. DNA double-stand breaks (DSBs) are one of the most deleterious type of DNA damage, which can be generated by ionizing radiation. DSBs are mainly repaired by either non-homologous end-joining or homologous recombination repair. In this study, we sought to reveal potential involvement of nuclear bodies in DSB repair. Among these, we focused on nuclear speckles that localize next to transcriptionally active regions. Mechanistically, we established that USP42, hitherto unidentified nuclear speckle factor, promoted homologous recombination repair.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、DSB修復、特に相同組換え修復、への影響を指標に核内構造体であるnuclear specklesを構成するタンパク質をスクリーニングした。その結果、複数の新規因子がDSB修復に正あるいは、負に寄与することが示唆され、nuclear specklesという核内空間の特異的な領域を占める構造体がゲノム安定性に寄与することが明らかになった。これは、核内構造体によって規定されるゲノム構造・機能がDSB修復に重要であることを示唆しており、新しい研究領域を切り開いたものであると言える。
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Report
(5 results)
Research Products
(48 results)
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[Journal Article] A novel nuclear speckle factor, USP42, promotes homologous recombination repair by resolving DNA double-strand break induced R-loop2019
Author(s)
Misaki Matsui, Ryo Sakasai, Masako Abe, Yusuke Kimura, Shoki Kajita, Wakana Torii, Yoko Katsuki, Masamichi Ishiai, Kuniyoshi Iwabuchi, Minoru Takata, Ryotaro Nishi
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Journal Title
DOI
Related Report
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[Journal Article] Thymine DNA glycosylase modulates the DNA damage response and gene expression by base excision repair-dependent and -independent mechanisms2017
Author(s)
Tomohumi Nakamura, Kouichi Murakami, Haruto Tada, Yoshihiko Uehara, Jumpei Nogami, Kazumitsu Maehara, Yasuyuki Ohkawa, Hisato Saitoh, Hideo Nishitani, Tetsuya Ono, Ryotaro Nishi, Masayuki Yokoi, Wataru Sakai, and Kaoru Sugasawa
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Journal Title
Genes to Cells
Volume: 22
Issue: 4
Pages: 392-405
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] BRCA1 directs the repair pathway to homologous recombination by promoting 53BP1 dephosphorylation2017
Author(s)
Mayu Isono, Atsuko Niimi, Takahiro Oike, Yoshihiko Hagiwara, Hiro Sato, Ryota Sekine, Yukari Yoshida, Shin-Ya Isobe, Chikashi Obuse, Ryotaro Nishi, Elena Petricci, Shinichiro Nakada, Takashi Nakano, Atsushi Shibata
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Journal Title
Cell Reports
Volume: 18
Issue: 2
Pages: 520-532
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Presentation] Regulatory mechanism resolving DNA double-strand break induced R-loop2019
Author(s)
Ryotaro Nishi, Misaki Matsui, Ryo Sakasai, Masako Abe, Yusuke Kimura, Shoki Kajita, Wakana Torii, Yoko Katsuki, Masamichi Ishiai, Kuniyoshi Iwabuchi, Minoru Takata
Organizer
日本放射線影響学会第62回大会
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[Presentation] A deubiquitylating enzyme, UCHL3, enhances non-homologous end-joining by regulating Ku ubiquitylation2017
Author(s)
Ryotaro Nishi, Paul Wijnhoven, Yusuke Kimura, Misaki Matsui, Keisuke Nakamura, Rebecca Konietny, Qian Wu, Toshiyuki Hori, Tom Blundell, Benedikt M Kessler and Stephen P Jackson
Organizer
The 33rd International Symposium of Radiation Biology Center （口頭発表）
Related Report
Int'l Joint Research
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[Presentation] 非相同末端再結合を制御する新規因子の解析2017
Author(s)
Ryotaro Nishi, Paul Wijnhoven, Yusuke Kimura, Misaki Matsui, Keisuke Nakamura, Rebecca Konietzny, Qian Wu, Toshiyuki Hori, Tom Blundell, Benedikt M Kessler, and Stephen P. Jackson
Organizer
第24回DNA複製・組換え・修復ワークショップ
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[Presentation] A deubiquitylating enzyme, UCHL3, enhances non-homologous end-joining by regulating Ku ubiquitylation2017
Author(s)
Ryotaro Nishi, Paul Wijnhoven, Yusuke Kimura, Misaki Matsui, Keisuke Nakamura, Rebecca Konietny, Qian Wu, Toshiyuki Hori, Tom Blundell, Benedikt M Kessler and Stephen P Jackson
Organizer
The 33rd International Symposium of Radiation Biology Center （ポスター発表）
Related Report
Int'l Joint Research
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