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The Dbf4/Drf1-dependent kinase (DDK) is required for the initiation of DNA replication in eukaryotes. Another protein, Claspin, mediates the activation of a cellular checkpoint response to stalled replication forks and is also a regulator of replication. In this study, we found that DDK phosphorylates Claspin in vitro and forms a nuclear complex containing Cdc7, Drf1, and Claspin in Xenopus egg extracts. In addition, purified Claspin and DDK are capable of a direct in vitro interaction. We identified a conserved binding site on Claspin required for its interaction with DDK. This site corresponds to the first of two sequence repeats in the Chk1-binding domain of Claspin. Furthermore, we have established that two amino acids in this motif, Asp(861) and Gln(866), are essential for the interaction between Claspin and DDK. We found that mutant forms of Claspin incapable of interacting with DDK are still able to associate with and activate Chk1 in response to DNA replication blockages. However, Claspin-depleted egg extracts that have been reconstituted with these mutants of Claspin undergo DNA replication more slowly. These findings suggest that the interaction of DDK with Claspin mediates a checkpoint-independent function of Claspin related to DNA replication.
Aparicio,
The human GINS complex associates with Cdc45 and MCM and is essential for DNA replication.
2009, Pubmed,
Xenbase
Aparicio,
The human GINS complex associates with Cdc45 and MCM and is essential for DNA replication.
2009,
Pubmed
,
Xenbase Arias,
Strength in numbers: preventing rereplication via multiple mechanisms in eukaryotic cells.
2007,
Pubmed Chini,
Repeated phosphopeptide motifs in human Claspin are phosphorylated by Chk1 and mediate Claspin function.
2006,
Pubmed
,
Xenbase Chini,
Human claspin is required for replication checkpoint control.
2003,
Pubmed
,
Xenbase Clarke,
DNA-dependent phosphorylation of Chk1 and Claspin in a human cell-free system.
2005,
Pubmed
,
Xenbase Gambus,
GINS maintains association of Cdc45 with MCM in replisome progression complexes at eukaryotic DNA replication forks.
2006,
Pubmed Hodgson,
Mrc1 and Tof1 regulate DNA replication forks in different ways during normal S phase.
2007,
Pubmed Jeong,
Phosphorylated claspin interacts with a phosphate-binding site in the kinase domain of Chk1 during ATR-mediated activation.
2003,
Pubmed
,
Xenbase Jiang,
Mammalian Cdc7-Dbf4 protein kinase complex is essential for initiation of DNA replication.
1999,
Pubmed Kastan,
Cell-cycle checkpoints and cancer.
2004,
Pubmed Katou,
S-phase checkpoint proteins Tof1 and Mrc1 form a stable replication-pausing complex.
2003,
Pubmed Kim,
Cdc7 kinase mediates Claspin phosphorylation in DNA replication checkpoint.
2008,
Pubmed Kumagai,
The Xenopus Chk1 protein kinase mediates a caffeine-sensitive pathway of checkpoint control in cell-free extracts.
1998,
Pubmed
,
Xenbase Kumagai,
Claspin and the activated form of ATR-ATRIP collaborate in the activation of Chk1.
2004,
Pubmed
,
Xenbase Kumagai,
Claspin, a novel protein required for the activation of Chk1 during a DNA replication checkpoint response in Xenopus egg extracts.
2000,
Pubmed
,
Xenbase Kumagai,
Repeated phosphopeptide motifs in Claspin mediate the regulated binding of Chk1.
2003,
Pubmed
,
Xenbase Kumagai,
A novel growth- and cell cycle-regulated protein, ASK, activates human Cdc7-related kinase and is essential for G1/S transition in mammalian cells.
1999,
Pubmed Kumagai,
Purification and molecular cloning of Plx1, a Cdc25-regulatory kinase from Xenopus egg extracts.
1996,
Pubmed
,
Xenbase Lee,
Claspin, a Chk1-regulatory protein, monitors DNA replication on chromatin independently of RPA, ATR, and Rad17.
2003,
Pubmed
,
Xenbase Lee,
Roles of replication fork-interacting and Chk1-activating domains from Claspin in a DNA replication checkpoint response.
2005,
Pubmed
,
Xenbase Lin,
Human Claspin works with BRCA1 to both positively and negatively regulate cell proliferation.
2004,
Pubmed
,
Xenbase Lou,
Mrc1 and DNA polymerase epsilon function together in linking DNA replication and the S phase checkpoint.
2008,
Pubmed Masai,
Phosphorylation of MCM4 by Cdc7 kinase facilitates its interaction with Cdc45 on the chromatin.
2006,
Pubmed Masai,
Cdc7 kinase complex: a key regulator in the initiation of DNA replication.
2002,
Pubmed Melo,
A unified view of the DNA-damage checkpoint.
2002,
Pubmed
,
Xenbase Montagnoli,
Drf1, a novel regulatory subunit for human Cdc7 kinase.
2002,
Pubmed Moyer,
Isolation of the Cdc45/Mcm2-7/GINS (CMG) complex, a candidate for the eukaryotic DNA replication fork helicase.
2006,
Pubmed Osborn,
Mrc1 is a replication fork component whose phosphorylation in response to DNA replication stress activates Rad53.
2003,
Pubmed Pacek,
Localization of MCM2-7, Cdc45, and GINS to the site of DNA unwinding during eukaryotic DNA replication.
2006,
Pubmed
,
Xenbase Petermann,
Claspin promotes normal replication fork rates in human cells.
2008,
Pubmed Roberts,
DNA replication in vertebrates requires a homolog of the Cdc7 protein kinase.
1999,
Pubmed
,
Xenbase Sar,
Human claspin is a ring-shaped DNA-binding protein with high affinity to branched DNA structures.
2004,
Pubmed
,
Xenbase Sheu,
Cdc7-Dbf4 phosphorylates MCM proteins via a docking site-mediated mechanism to promote S phase progression.
2006,
Pubmed Silva,
Xenopus CDC7/DRF1 complex is required for the initiation of DNA replication.
2006,
Pubmed
,
Xenbase Ström,
Postreplicative formation of cohesion is required for repair and induced by a single DNA break.
2007,
Pubmed Szyjka,
Mrc1 is required for normal progression of replication forks throughout chromatin in S. cerevisiae.
2005,
Pubmed Takahashi,
Cdc7-Drf1 is a developmentally regulated protein kinase required for the initiation of vertebrate DNA replication.
2005,
Pubmed
,
Xenbase Takahashi,
Cdc7-Drf1 kinase links chromosome cohesion to the initiation of DNA replication in Xenopus egg extracts.
2008,
Pubmed
,
Xenbase Takeda,
DNA replication and progression through S phase.
2005,
Pubmed Tenca,
Cdc7 is an active kinase in human cancer cells undergoing replication stress.
2007,
Pubmed Tourrière,
Mrc1 and Tof1 promote replication fork progression and recovery independently of Rad53.
2005,
Pubmed Tsuji,
Essential role of phosphorylation of MCM2 by Cdc7/Dbf4 in the initiation of DNA replication in mammalian cells.
2006,
Pubmed Tsuji,
The role of Dbf4/Drf1-dependent kinase Cdc7 in DNA-damage checkpoint control.
2008,
Pubmed
,
Xenbase Walter,
Evidence for sequential action of cdc7 and cdk2 protein kinases during initiation of DNA replication in Xenopus egg extracts.
2000,
Pubmed
,
Xenbase Yanow,
Xenopus Drf1, a regulator of Cdc7, displays checkpoint-dependent accumulation on chromatin during an S-phase arrest.
2003,
Pubmed
,
Xenbase Yoo,
Site-specific phosphorylation of a checkpoint mediator protein controls its responses to different DNA structures.
2006,
Pubmed
,
Xenbase Zou,
Assembly of a complex containing Cdc45p, replication protein A, and Mcm2p at replication origins controlled by S-phase cyclin-dependent kinases and Cdc7p-Dbf4p kinase.
2000,
Pubmed
