Mechanism of intra-nuclear localization of fission yeast chromosome

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K14450
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Molecular biology
• Research Institution: Osaka University
• Principal Investigator: Masukata Hisao 大阪大学, その他部局等, 名誉教授 (00199689)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: テロメア / 複製開始点 / 複製タイミング / 分裂酵母 / shelterin

Outline of Final Research Achievements

For faithful duplication of genetic information, DNA replication initiates from many distinct sites on eukaryotic chromosomes in a manner to be regulated by a spatiotemporal program, although the molecular mechanisms of regulation has not been uncovered. We discovered that the higher-order chromatin communication of the telomeres and internal late replication origin plays important role in replication-timing control. Using LacI-GFP fluorescent protein bound to lacO repeat inserted nearby replication origins in fission yeast Shizosaccharomyces pombe, we found that late replication origins are localized at the nuclear periphery and adjacent to telomeres especially in G1/S phase when replication-timing is determined. Telomere-binding protein complex “shelterin” is required for telomere-association of the internal replication origins, although the nuclear peripheral localization is not important. These finding provide insight into a novel mechanism of replication control by telomeres.

Free Research Field

分子遺伝学

Academic Significance and Societal Importance of the Research Achievements

これまで複製開始制御と核内配置の関係は明らかにされていなかったが、目印となる蛍光タンパク質を特定の複製開始点に結合させることにより、生きた酵母細胞で複製開始点の高解像度観察が可能になった。本研究は、染色体末端テロメアが遠く離れた染色体内部とコミュニケーションするしくみを明らかにしたことになり、将来テロメアが遠隔制御する疾患原因遺伝子の発見ならびに疾患の予防につながる可能性がある。