Cdc7-Drf1 kinase links chromosome cohesion to the initiation of DNA replication in Xenopus egg extracts Journal Article


Authors: Takahashi, T. S.; Basu, A.; Bermudez, V.; Hurwitz, J.; Walter, J. C.
Article Title: Cdc7-Drf1 kinase links chromosome cohesion to the initiation of DNA replication in Xenopus egg extracts
Abstract: To establish functional cohesion between replicated sister chromatids, cohesin is recruited to chromatin before S phase. Cohesin is loaded onto chromosomes in the G1 phase by the Scc2-Scc4 complex, but little is known about how Scc2-Scc4 itself is recruited to chromatin. Using Xenopus egg extracts as a vertebrate model system, we showed previously that the chromatin association of Scc2 and cohesin is dependent on the prior establishment of prereplication complexes (pre-RCs) at origins of replication. Here, we report that Scc2-Scc4 exists in a stable complex with the Cdc7-Drf1 protein kinase (DDK), which is known to bind pre-RCs and activate them for DNA replication. Immunodepletion of DDK from Xenopus egg extracts impairs chromatin association of Scc2-Scc4, a defect that is reversed by wild-type, but not catalytically inactive DDK. A complex of Scc4 and the N terminus of Scc2 is sufficient for chromatin loading of Scc2-Scc4, but not for cohesin recruitment. These results show that DDK is required to tether Scc2-Scc4 to pre-RCs, and they underscore the intimate link between early steps in DNA replication and cohesion. © 2008 by Cold Spring Harbor Laboratory Press.
Keywords: nonhuman; dna replication; protein function; mitosis; cohesin; animal cell; chromosome; animals; cell cycle proteins; chromosomal proteins, non-histone; oocytes; biological model; protein protein interaction; protein; protein stability; wild type; vertebrata; amino terminal sequence; chromatin; protein-serine-threonine kinases; nucleotide sequence; enzyme inactivation; immunoblotting; sister chromatid exchange; immunoassay; catalysis; enzyme binding; vertebrate; protein kinase; cell extracts; xenopus; oocyte development; xenopus laevis; cohesion; rabbits; xenopus proteins; cdc7-drf1; scc2-scc4; cdc7 drf1 protein kinase; protein scc2; protein scc4
Journal Title: Genes and Development
Volume: 22
Issue: 14
ISSN: 0890-9369
Publisher: Cold Spring Harbor Laboratory Press  
Date Published: 2008-07-15
Start Page: 1894
End Page: 1905
Language: English
DOI: 10.1101/gad.1683308
PUBMED: 18628396
PROVIDER: scopus
PMCID: PMC2492736
DOI/URL:
Notes: --- - "Cited By (since 1996): 23" - "Export Date: 17 November 2011" - "CODEN: GEDEE" - "Molecular Sequence Numbers: GENBANK: NP_593137, TC260044, TC290672, EU747648;" - "Source: Scopus"
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  1. Abhijit Basu
    1 Basu
  2. Jerard Hurwitz
    206 Hurwitz