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

Tatsuro S. Takahashi, Abhijit Basu, Vladimir Bermudez, Jerard Hurwitz, Johannes C. Walter

Research output: Contribution to journalArticlepeer-review

85 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1894-1905
Number of pages12
JournalGenes and Development
Volume22
Issue number14
DOIs
Publication statusPublished - Jul 15 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Developmental Biology

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