Novel machinery of maintenance of genomic integrity by multinuclease complexes

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K06784
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 45010:Genetics-related
• Research Institution: Kindai University
• Principal Investigator: Saito Takamune 近畿大学, 生物理工学部, 講師 (60741494)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 減数分裂 / 線虫 / ファンコニ貧血 / 交差型組換え

Outline of Final Research Achievements

We tried to identify the suppressor mutations for him-18, which is a C. elegans homolog of the Fanconi anemia gene SLX4. We succeeded to narrow down the candidates to seven genes in the strain #249 and six genes in the strain #296. The amount of DNA double-strand breaks was reduced in him-17 mutants and they localized even in the central region of chromosomes. Crossover distribution is limited to the one of the arm regions of chromosomes in wild-type. Crossover distribution shifted to the central region of the chromosome in him-17 mutants. From those results, it was clarified that HIM-17 has a function of inducing DNA double-strand breaks among the chromosome arms and promoting crossover in the arm regions and suppressing crossover in the central region of the chromosomes. We also clarified that HIM-17 functions for accurate chromosome segregation during meiosis I by regulation of the chromosomal localization of the kinase and the phosphatases.

Free Research Field

分子遺伝学

Academic Significance and Societal Importance of the Research Achievements

him-18/SLX4のサプレッサー変異は国内外でも同定されておらず、候補が6-7遺伝子に絞り込まれたことは意義のある成果といえる。今後の展望としては、候補遺伝子を一つに絞り込み、患者の細胞を用いてファンコニ貧血治療への応用を探る事になる。
交差分布の制御機構に関して、制限酵素処理を省く事ができる実験系を確立でき、大幅な手間と時間の短縮に貢献した。him-17変異体では、ヒストンH3K9のジメチル化が減少し、DNA二重鎖切断の染色体腕部への偏りが解除された。結果として交差分布が染色体中央にシフトした事は、染色体のエピジェネティックな変化が交差分布に影響を与えうる事を示したと言える。