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Claspin recruits Cdc7 kinase for initiation of DNA replication in human cells
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 kn...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4945878/ https://www.ncbi.nlm.nih.gov/pubmed/27401717 http://dx.doi.org/10.1038/ncomms12135 |
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author | Yang, Chi-Chun Suzuki, Masahiro Yamakawa, Shiori Uno, Syuzi Ishii, Ai Yamazaki, Satoshi Fukatsu, Rino Fujisawa, Ryo Sakimura, Kenji Tsurimoto, Toshiki Masai, Hisao |
author_facet | Yang, Chi-Chun Suzuki, Masahiro Yamakawa, Shiori Uno, Syuzi Ishii, Ai Yamazaki, Satoshi Fukatsu, Rino Fujisawa, Ryo Sakimura, Kenji Tsurimoto, Toshiki Masai, Hisao |
author_sort | Yang, Chi-Chun |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4945878 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-49458782016-09-06 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 Nat Commun Article 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. Nature Publishing Group 2016-07-12 /pmc/articles/PMC4945878/ /pubmed/27401717 http://dx.doi.org/10.1038/ncomms12135 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article 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 |
title | Claspin recruits Cdc7 kinase for initiation of DNA replication in human cells |
title_full | Claspin recruits Cdc7 kinase for initiation of DNA replication in human cells |
title_fullStr | Claspin recruits Cdc7 kinase for initiation of DNA replication in human cells |
title_full_unstemmed | Claspin recruits Cdc7 kinase for initiation of DNA replication in human cells |
title_short | Claspin recruits Cdc7 kinase for initiation of DNA replication in human cells |
title_sort | claspin recruits cdc7 kinase for initiation of dna replication in human cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4945878/ https://www.ncbi.nlm.nih.gov/pubmed/27401717 http://dx.doi.org/10.1038/ncomms12135 |
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