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7057470 
Journal Article 
Perpetuating the double helix: molecular machines at eukaryotic DNA replication origins 
Méndez, J; Stillman, B; , 
2003 
Yes 
BioEssays
ISSN: 0265-9247
EISSN: 1521-1878 
English 
The hardest part of replicating a genome is the beginning. The first step of DNA replication (called "initiation") mobilizes a large number of specialized proteins ("initiators") that recognize specific sequences or structural motifs in the DNA, unwind the double helix, protect the exposed ssDNA, and recruit the enzymatic activities required for DNA synthesis, such as helicases, primases and polymerases. All of these components are orderly assembled before the first nucleotide can be incorporated. On the occasion of the 50th anniversary of the discovery of the DNA structure, we review our current knowledge of the molecular mechanisms that control initiation of DNA replication in eukaryotic cells, with particular emphasis on the recent identification of novel initiator proteins. We speculate how these initiators assemble molecular machines capable of performing specific biochemical tasks, such as loading a ring-shaped helicase onto the DNA double helix.