Sex chromosome specific-mechanisms to regulate DNA damage response during mammalian male meiosis

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20635
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0701:Biology at molecular to cellular levels, and related fields
• Research Institution: Kumamoto University
• Principal Investigator: Abe Hironori 熊本大学, 発生医学研究所, 特任助教 (20914964)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 減数分裂 / 精子形成 / DNA損傷応答

Outline of Final Research Achievements

In male meiosis, XY chromosomes, which have a non-homologous pair, undergo Meiotic Sex Chromosome Inactivation (MSCI) where genes are simultaneously inactivated. Failure of MSCI induces the loss of spermatocytes, indicating that MSCI is a crucial phenomenon for the success of meiosis. However, the molecular mechanisms of MSCI are poorly understood. We have demonstrated that DNA Damage Response (DDR) signaling plays an important role in the initiation and maintenance of sex chromosome inactivation. In this study, we have developed a new mouse tool to elucidate the molecular mechanisms that specifically activate DDR signaling on sex chromosomes. Advancing this research is expected to lead to the discovery of novel DDR signal regulatory factors specific to male meiosis.

Free Research Field

減数分裂

Academic Significance and Societal Importance of the Research Achievements

DDR シグナルは損傷 DNA によって活性化されるが、性染色体では損傷 DNA が存在しなくても DDR シグナルが継続的に活性化される。このような現象は減数分裂に特異的であり、分子機構を理解することでその生物学的意義に迫ることができるようになる。減数分裂の失敗は不妊に直結することから、その制御機構の詳細な理解は生殖医療への貢献が期待できる。また DDR シグナルは体細胞分裂の制御にも極めて重要であり、その制御機構の破綻は細胞のガン化の引き金となる。そのため、本研究で開発した新規マウスツールはがん発生機序の解明やがん克服に向けた創薬研究における新規標的因子の探索への応用が期待される。