Molecular basis of subtelomeric recombination in meiosis

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15129
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 44020:Developmental biology-related
• Research Institution: National Institute of Genetics
• Principal Investigator: Imai Yukiko 国立遺伝学研究所, 遺伝形質研究系, 特任研究員 (00814782)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 減数分裂 / 組換え / ゼブラフィッシュ

Outline of Final Research Achievements

Meiotic recombination plays an essential role in chromosome segregation during gametogenesis and promotes genome shuffling. Meiotic recombination is initiated by programed DNA double-strand breads (DSBs) that occur at discrete regions of a genome. In human and zebrafish males, DSBs are preferentially occur near at the end of chromosomes in unknown mechanisms. In this study, function and localization of Iho1 were analyzed in zebrafish. Analyses using iho1 mutant zebrafish demonstrated that Iho1 is required for proper gametogenesis in both males and females. In zebrafish spermatocytes, Iho1 localizes near telomeres prior to DSB formation and is essential for DSB formation. Cytological analyses using meiotic mutant zebrafish lines supports an idea that subtelomeric localization of Iho1 occurs dependently of a component of chromosomal axes, but not the formation of telomere bouquet structure or Hormad1.

Free Research Field

減数分裂

Academic Significance and Societal Importance of the Research Achievements

組換えの理解は、ヒトにおける不妊・染色体異常や、生物の多様性を理解する上で重要な意義を持つ。DSBは組換えに必須である一方で、細胞に重篤な損傷をもたらす恐れがあり、厳密な制御を受ける。ヒトの精子形成にみられるサブテロメア型のDSB形成はマウスでは顕著でなく、研究モデルの欠如から、その分子基盤は全く明らかになっていなかった。本研究は、サブテロメア型のDSB形成メカニズムに着目した初めての研究であり、"ヒトの組換えメカニズムの理解"と"新規組換えメカニズムの理解"という観点から、重要な意義を持つ。