Distinction of DSB repair pathways in mitosis and meiosis

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H03711
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Genetics/Chromosome dynamics
• Research Institution: The University of Tokyo
• Principal Investigator: Ohta Kunihiro 東京大学, 大学院総合文化研究科, 教授 (90211789)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 減数分裂 / 組換え / 染色体 / ゲノム再編成

Outline of Final Research Achievements

DNA double strand breaks (DSBs) cause various chromosomal rearrangements, leading to diseases such as cancer and cell senescence. On the other hand, DSB formation by Spo11 during meiosis occurs at recombination hotspots, but chromosomal translocations are suppressed, resulting in conservative genomic alterations. Application of TAQing system, a gross genome rearrangement-inducing system, to yeast cells in mitosis and meiosis revealed distinct effects on genome rearrangements. While rare translocations and copy number fluctuations occur during meiosis, they are often detected in TAQed mitotic cells. The spo11 deletion strain TAQed in meiosis failed to complete normal segregation of homologous chromosomes, suggesting that DNA cleavage by Spo11 was more important than expected.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

今回の解析により、有糸分裂期に生じたＤＮＡ切断は、転座やコピー数変動などの染色体異常を誘発しやすいが、減数分裂期のSpo11によるDSB形成は何らかの機構でそのような異常を抑制していることが示唆された。この結果は、線虫や分裂酵母の先行研究からは予測できなかったものであり、Spo11によるDSB形成の未知の役割が新たに示されたことになる。また、有糸分裂期のDSB形成で生じる染色体再編成は、がん細胞内で生じる変化に極めて近いものであり、発がんにおけるＤＮＡ切断の役割についても重要な示唆が得られた。