Understanding the mechanisms by which Ctf4 protein suppresses repair of DNA double-strand breaks by homologous recombination

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K06597
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43050:Genome biology-related
• Research Institution: National Institute of Genetics (2023); The University of Tokyo (2020-2022)
• Principal Investigator: Mariko Sasaki 国立遺伝学研究所, 新分野創造センター, 准教授 (50722013)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: Ctf4 / DNA複製阻害 / DNA二本鎖切断 / 相同組換え / ゲノム不安定化

Outline of Final Research Achievements

In this research project, I aimed to elucidate the mechanism by which the DNA replication factor Ctf4 protein suppresses homologous recombination-mediated DSB repair, using the ribosomal RNA gene (rDNA) region of budding yeast. By performing chromatin immunoprecipitation experiments, I identified homologous recombination factors and DNA replication factors whose binding to the DSB sites is altered in Ctf4-deficient cells. Additionally, I found that the interaction between Ctf4 and Mms22 proteins is important for suppressing rDNA instability.

Free Research Field

ゲノム生物学

Academic Significance and Societal Importance of the Research Achievements

DNA二本鎖切断は、DNA複製の途中で発生することが多く、その不正確な修復はゲノム不安定化を誘導し、がんなどの様々な疾患を引き起こす原因となる。本研究では、DNA複製阻害時に生じるDNA二本鎖切断修復に関与するCtf4タンパク質の作用機構の一端を明らかにすることができた。CTF4遺伝子はヒト細胞でも保存されている。よって、本研究で得られた知見をもとに、ヒト細胞で起こるDNA二本鎖切断修復機構の解明に向けた研究に発展させることができる。