【第66回がん研先端研究セミナー(1月19日)のお知らせ「How do cells remove the DNA replication machinery from mitotic chromosomes? 」Ryo Fujisawa (The MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, United Kingdom)】
2024年01月05日
第36回がん研先端研究セミナー(1月19日)のお知らせ
演題：How do cells remove the DNA replication machinery from mitotic chromosomes?
演者：Ryo Fujisawa (The MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, United Kingdom)
抄録：
Chromosomal DNA is replicated by the DNA replication machinery (replisome) during the S-phase of the cell cycle prior to mitosis. Recent studies revealed that cells, especially with a large genome size, often enter into mitosis before completing DNA replication. Works with worm, frog and mammalian cells demonstrated that there is a dedicated mechanism to remove replisomes that remain on mitotic chromosomes, which relies on a replisome-associating E3 ligase TRAIP and the p97/VCP unfoldase. This TRAIP- and p97-dependent mitotic replisome disassembly is thought to enable the rapid processing of sites of incomplete DNA replication before chromosome segregation, known as Mitotic DNA synthesis (MiDAS). Curiously, TRAIP constitutively binds to replisome and supports replisome progression during S-phase, whereas in mitosis, it drives replisome disassembly. How mitotic cells switch TRAIP’s action for mitotic replisome disassembly is unclear.
We found that, in mitosis, CDK-phosphorylated TRAIP forms a complex with Polε (DNA Polymerase Epsilon) and a poorly-characterized SWI/SNF ATPase called TTF2 (Transcription Termination Factor 2). TTF2 was previously reported to be a cytoplasmic factor that accumulates on mitotic chromatin and displaces RNA polymerase II. Mechanistically, Polε and TTF2 reposition TRAIP for polyubiquitylation of replisome on mitotic chromatin, leading to replisome disassembly by p97. With these unpublished data, I will discuss how mitotic cells deal with molecular machines for replication and transcription and how their misregulation damages cells.
日時：日時：2024年1月19日（金）15：30 〜 16：30
場所：吉田記念講堂
演題：How do cells remove the DNA replication machinery from mitotic chromosomes?
演者：Ryo Fujisawa (The MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, United Kingdom)
抄録：
Chromosomal DNA is replicated by the DNA replication machinery (replisome) during the S-phase of the cell cycle prior to mitosis. Recent studies revealed that cells, especially with a large genome size, often enter into mitosis before completing DNA replication. Works with worm, frog and mammalian cells demonstrated that there is a dedicated mechanism to remove replisomes that remain on mitotic chromosomes, which relies on a replisome-associating E3 ligase TRAIP and the p97/VCP unfoldase. This TRAIP- and p97-dependent mitotic replisome disassembly is thought to enable the rapid processing of sites of incomplete DNA replication before chromosome segregation, known as Mitotic DNA synthesis (MiDAS). Curiously, TRAIP constitutively binds to replisome and supports replisome progression during S-phase, whereas in mitosis, it drives replisome disassembly. How mitotic cells switch TRAIP’s action for mitotic replisome disassembly is unclear.
We found that, in mitosis, CDK-phosphorylated TRAIP forms a complex with Polε (DNA Polymerase Epsilon) and a poorly-characterized SWI/SNF ATPase called TTF2 (Transcription Termination Factor 2). TTF2 was previously reported to be a cytoplasmic factor that accumulates on mitotic chromatin and displaces RNA polymerase II. Mechanistically, Polε and TTF2 reposition TRAIP for polyubiquitylation of replisome on mitotic chromatin, leading to replisome disassembly by p97. With these unpublished data, I will discuss how mitotic cells deal with molecular machines for replication and transcription and how their misregulation damages cells.
日時：日時：2024年1月19日（金）15：30 〜 16：30
場所：吉田記念講堂
