Claspin recruits Cdc7 kinase for initiation of DNA replication in human cells

Chi Chun Yang, Masahiro Suzuki, Shiori Yamakawa, Syuzi Uno, Ai Ishii, Satoshi Yamazaki, Rino Fukatsu, Ryo Fujisawa, Kenji Sakimura, Toshiki Tsurimoto, Hisao Masai

研究成果: ジャーナルへの寄稿記事

10 引用 (Scopus)

抄録

Claspin transmits replication stress signal from ATR to Chk1 effector kinase as a mediator. It also plays a role in efficient replication fork progression during normal growth. Here we have generated conditional knockout of Claspin and show that Claspin knockout mice are dead by E12.5 and Claspin knockout mouse embryonic fibroblast (MEF) cells show defect in S phase. Using the mutant cell lines, we report the crucial roles of the acidic patch (AP) near the C terminus of Claspin in initiation of DNA replication. Cdc7 kinase binds to AP and this binding is required for phosphorylation of Mcm. AP is involved also in intramolecular interaction with a N-terminal segment, masking the DNA-binding domain and a newly identified PIP motif, and Cdc7-mediated phosphorylation reduces the intramolecular interaction. Our results suggest a new role of Claspin in initiation of DNA replication during normal S phase through the recruitment of Cdc7 that facilitates phosphorylation of Mcm proteins.

元の言語英語
記事番号12135
ジャーナルNature communications
7
DOI
出版物ステータス出版済み - 7 12 2016

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phosphorylation
Phosphorylation
knockout mice
DNA Replication
Phosphotransferases
deoxyribonucleic acid
Cells
S Phase
Knockout Mice
DNA
effectors
forks
fibroblasts
Fibroblasts
masking
cultured cells
progressions
interactions
proteins
Cell Line

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

これを引用

Yang, C. C., Suzuki, M., Yamakawa, S., Uno, S., Ishii, A., Yamazaki, S., ... Masai, H. (2016). Claspin recruits Cdc7 kinase for initiation of DNA replication in human cells. Nature communications, 7, [12135]. https://doi.org/10.1038/ncomms12135

Claspin recruits Cdc7 kinase for initiation of DNA replication in human cells. / Yang, Chi Chun; Suzuki, Masahiro; Yamakawa, Shiori; Uno, Syuzi; Ishii, Ai; Yamazaki, Satoshi; Fukatsu, Rino; Fujisawa, Ryo; Sakimura, Kenji; Tsurimoto, Toshiki; Masai, Hisao.

:: Nature communications, 巻 7, 12135, 12.07.2016.

研究成果: ジャーナルへの寄稿記事

Yang, CC, Suzuki, M, Yamakawa, S, Uno, S, Ishii, A, Yamazaki, S, Fukatsu, R, Fujisawa, R, Sakimura, K, Tsurimoto, T & Masai, H 2016, 'Claspin recruits Cdc7 kinase for initiation of DNA replication in human cells', Nature communications, 巻. 7, 12135. https://doi.org/10.1038/ncomms12135
Yang CC, Suzuki M, Yamakawa S, Uno S, Ishii A, Yamazaki S その他. Claspin recruits Cdc7 kinase for initiation of DNA replication in human cells. Nature communications. 2016 7 12;7. 12135. https://doi.org/10.1038/ncomms12135
Yang, Chi Chun ; Suzuki, Masahiro ; Yamakawa, Shiori ; Uno, Syuzi ; Ishii, Ai ; Yamazaki, Satoshi ; Fukatsu, Rino ; Fujisawa, Ryo ; Sakimura, Kenji ; Tsurimoto, Toshiki ; Masai, Hisao. / Claspin recruits Cdc7 kinase for initiation of DNA replication in human cells. :: Nature communications. 2016 ; 巻 7.
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abstract = "Claspin transmits replication stress signal from ATR to Chk1 effector kinase as a mediator. It also plays a role in efficient replication fork progression during normal growth. Here we have generated conditional knockout of Claspin and show that Claspin knockout mice are dead by E12.5 and Claspin knockout mouse embryonic fibroblast (MEF) cells show defect in S phase. Using the mutant cell lines, we report the crucial roles of the acidic patch (AP) near the C terminus of Claspin in initiation of DNA replication. Cdc7 kinase binds to AP and this binding is required for phosphorylation of Mcm. AP is involved also in intramolecular interaction with a N-terminal segment, masking the DNA-binding domain and a newly identified PIP motif, and Cdc7-mediated phosphorylation reduces the intramolecular interaction. Our results suggest a new role of Claspin in initiation of DNA replication during normal S phase through the recruitment of Cdc7 that facilitates phosphorylation of Mcm proteins.",
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AU - Ishii, Ai

AU - Yamazaki, Satoshi

AU - Fukatsu, Rino

AU - Fujisawa, Ryo

AU - Sakimura, Kenji

AU - Tsurimoto, Toshiki

AU - Masai, Hisao

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