2. Academic Validation
  3. Claspin recruits Cdc7 kinase for initiation of DNA replication in human cells

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

  • Nat Commun. 2016 Jul 12;7:12135. doi: 10.1038/ncomms12135.
Chi-Chun Yang 1,  Masahiro Suzuki 1,  Shiori Yamakawa 1,  Syuzi Uno 1,  Ai Ishii 1,  Satoshi Yamazaki 1,  Rino Fukatsu 1,  Ryo Fujisawa 2,  Kenji Sakimura 3,  Toshiki Tsurimoto 2,  Hisao Masai 1
Affiliations

Affiliations

  • 1 Department of Genome Medicine, Tokyo Metropolitan Institute of Medical Science, 4-6-1 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
  • 2 Department of Biology, Faculty of Science, Kyushu University 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan.
  • 3 Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan.
PMID: 27401717 DOI: 10.1038/ncomms12135
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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