Study on the mechanism for homologous chromosome pairing by HORMAD1

• Project/Area Number: 17K15392
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Integrative animal science
• Research Institution: The University of Tokyo
• Principal Investigator: Fujiwara Yasuhiro 東京大学, 定量生命科学研究所, 助教 (50793064)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 減数分裂 / HORMAD1相互作用因子 / 細胞・組織 / 遺伝学

Outline of Final Research Achievements

Gametes such as sperm and egg are produced through a specialized cell divisions called meiosis. During this process, homologous chromosomes pair and exchange part of their genetic information by homologous recombination. It is know that there is a mechanism which monitor if homologous chromosomes pair correctly. However, it has been elusive how factors responsible for this mechanism, such as HORMAD1, are recruited to where chromosomes pair. In this study, it was revealed that meiotic cohesin proteins play a key role in recruitment of HORMAD1 to the chromosome axis.

Academic Significance and Societal Importance of the Research Achievements

今回の成果はマウスを用いて検証されたが、ヒトの生殖細胞でも同じくコヒーシンやHORMAD1タンパク質が働いている。この仕組みが正常に働かなければ減数分裂組換え反応がうまく起こらなくなるため、精子・卵子形成が著しく低下し不妊となってしまう。ヒトの不妊症は原因が不明とされる症例が多いことが知られているため、今回の発見は、卵子・精子形成不全を示す不妊症の病態の解明に資することが期待される。

Research Products

• [Int'l Joint Research] ヨーテボリ大学(スウェーデン)
• [Int'l Joint Research] ヨーテボリ大学(スウェーデン)
• [Int'l Joint Research] ジャクソン研究所(米国)
• [Journal Article] Meiotic cohesins mediate initial loading of HORMAD1 to the chromosomes and coordinate SC formation during meiotic prophase (2020)
  • Author(s): Fujiwara Yasuhiro、Horisawa-Takada Yuki、Inoue Erina、Tani Naoki、Shibuya Hiroki、Fujimura Sayoko、Kariyazono Ryo、Sakata Toyonori、Ohta Kunihiro、Araki Kimi、Okada Yuki、Ishiguro Kei-ichiro
  • Journal Title: PLOS Genetics Volume: 16 Issue: 9 Pages: e1009048-e1009048
  • DOI: 10.1371/journal.pgen.1009048
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The BRCA2-MEILB2-BRME1 complex governs meiotic recombination and impairs the mitotic BRCA2-RAD51 axis (2020)
  • Author(s): Jingjing Zhang, Manickam Gurusaran, Yasuhiro Fujiwara, Manickam Gurusaran, Kexin Zhang, Meriem Echbarthi, Egor Vorontsov, Rui Guo, Devon F. Pendlebury, Intekhab Alam, Gabriel Livera, Martini Emmanuelle, P. Jeremy Wang, Jayakrishnan Nandakumar, Owen R. Davies, and Hiroki Shibuya
  • Journal Title: Nature Communications Volume: 11(1) Issue: 1 Pages: 2055-2055
  • DOI: 10.1038/s41467-020-15954-x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A meiosis-specific BRCA2 binding protein recruits recombinases to DNA double-strand breaks to ensure homologous recombination (2019)
  • Author(s): Zhang Jingjing、Fujiwara Yasuhiro、Yamamoto Shohei、Shibuya Hiroki
  • Journal Title: Nature Communications Volume: 10 Issue: 1 Pages: 722-722
  • DOI: 10.1038/s41467-019-08676-2
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Uncoupling of transcriptomic and cytological differentiation in mouse spermatocytes with impaired meiosis (2019)
  • Author(s): Fine Alexander D.、Ball Robyn L.、Fujiwara Yasuhiro、Handel Mary Ann、Carter Gregory W.
  • Journal Title: Molecular Biology of the Cell Volume: 30 Issue: 5 Pages: 717-728
  • DOI: 10.1091/mbc.e18-10-0681
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Hybrid sterility with meiotic metaphase arrest in intersubspecific mouse crosses. (2019)
  • Author(s): Nishino R, Petri S, Handel MA, Kunieda T, Fujiwara Y.
  • Journal Title: J Hered. Volume: 110 Issue: 2 Pages: 183-193
  • DOI: 10.1093/jhered/esy060
  • NAID: 130007485879
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Dissecting the telomere-inner nuclear membrane interface formed in meiosis (2017)
  • Author(s): Pendlebury Devon F、Fujiwara Yasuhiro、Tesmer Valerie M、Smith Eric M、Shibuya Hiroki、Watanabe Yoshinori、Nandakumar Jayakrishnan
  • Journal Title: Nat Struct Mol Biol Volume: 24 Issue: 12 Pages: 1064-1072
  • DOI: 10.1038/nsmb.3493
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Meiotic cohesins mediate initial chromatin loading of HORMAD1 and coordinate SC formation during meiotic prophase in mouse (2020)
  • Author(s): Yasuhiro Fujiwara, Yuki Horisawa-Takada, Naoki Tani, Hiroki Shibuya, Erina Inoue, Kimi Araki, Yuki Okada and Kei-ichiro Ishiguro
  • Organizer: Cold Spring Harbor Laboratory Meeting Germ Cell
  • Int'l Joint Research
• [Presentation] 減数分裂前期でのHORMAD１とコヒーシンによるクロマチンの制御 (2019)
  • Author(s): 藤原靖浩
  • Organizer: 2019遺伝研研究会 有性生殖に関わる染色体・核動態に関する研究会
  • Invited
• [Presentation] A HORMAD1-RAD21L complex is required for initial homolog recognition and pairing in mouse spermatocytes (2018)
  • Author(s): 藤原靖浩, 澁谷大輝, 岡田由紀, 渡邊嘉典, 石黒啓一郎
  • Organizer: 第41回日本分子生物学会大会
• [Presentation] Hybrid sterility with meiotic metaphase arrest in intersubspecific mouse crosses (2018)
  • Author(s): Yasuhiro Fujiwara, Risako Nishino, Sabrina Petri, Mary Ann Handel, Tetsuo Kunieda
  • Organizer: 第111回 日本繁殖生物学会大会