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

doi:10.1038/ncomms12135

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

Biology, Faculty of Science

Research output: Contribution to journal › Article › peer-review

31 Citations (Scopus)

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.

Original language	English
Article number	12135
Journal	Nature communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms12135
Publication status	Published - Jul 12 2016

All Science Journal Classification (ASJC) codes

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

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title = "Claspin recruits Cdc7 kinase for initiation of DNA replication in human cells",

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.",

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

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T1 - Claspin recruits Cdc7 kinase for initiation of DNA replication in human cells

AU - Yang, Chi Chun

AU - Suzuki, Masahiro

AU - Yamakawa, Shiori

AU - Uno, Syuzi

AU - Ishii, Ai

AU - Yamazaki, Satoshi

AU - Fukatsu, Rino

AU - Fujisawa, Ryo

AU - Sakimura, Kenji

AU - Tsurimoto, Toshiki

AU - Masai, Hisao

PY - 2016/7/12

Y1 - 2016/7/12

N2 - 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.

AB - 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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JO - Nature Communications

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ER -

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

Abstract

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