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REVIEW: Initiation of DNA Replication in Eukaryotes Is an Intriguing Cascade of Protein Interactions

N. P. Sharova* and E. B. Abramova

Kol'tsov Institute of Developmental Biology, Russian Academy of Sciences, ul. Vavilova 26, Moscow, 117808 Russia; fax: (095) 135-8012; E-mail: nsharova@proxima.idb.ac.ru

* To whom correspondence should be addressed.

Received February 12, 2002; Revision received March 28, 2002
Initiation of eukaryotic DNA replication is a complex process including the recognition of initiation sites on DNA, multi-step DNA preparation for duplication, and assembly of multi-protein complexes capable of beginning DNA synthesis at initiation sites. The process starts at the late M phase and lasts till the appropriate time of the S phase for each initiation site. A chain of interesting interactions between Orc1p-6p, Cdc6p, Mcm2p-7p, Mcm10p, Cdt1, Cdc45p, Dbf4/Cdc7p, RPA, and DNA polymerase alpha takes place during this period. The sequence of these interactions is controlled by cyclin-dependent kinases, as well as by ubiquitin-dependent proteolysis in the proteasome. This review summarizes the data on proteins initiating DNA replication and factors controlling their activities.
KEY WORDS: initiation of DNA replication, pre-replication complex, replication complex, control over DNA replication initiation