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 |
| 巻 | 7 |
| DOI | |
| 出版物ステータス | 出版済み - 7 12 2016 |
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All Science Journal Classification (ASJC) codes
- Chemistry(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Physics and Astronomy(all)
これを引用
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
}
TY - JOUR
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.
UR - http://www.scopus.com/inward/record.url?scp=84978864878&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84978864878&partnerID=8YFLogxK
U2 - 10.1038/ncomms12135
DO - 10.1038/ncomms12135
M3 - Article
C2 - 27401717
AN - SCOPUS:84978864878
VL - 7
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 12135
ER -