title: Perpetuating the double helix: molecular machines at eukaryotic DNA replication origins.
abstract: 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.
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA. mendezj@cshl.edu
authors.forename: Juan
authors.initials: J
authors.lastname: Méndez
authors.forename: Bruce
authors.initials: B
authors.lastname: Stillman
mesh_terms: D000818:Animals; D004247:DNA / Q000737:chemistry*; D004265:DNA Helicases / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000737:chemistry; D019143:Evolution, Molecular; D005656:Fungal Proteins / Q000378:metabolism; D005821:Genetic Techniques; D006801:Humans; D008954:Models, Biological; D008957:Models, Genetic; D018741:Replication Origin; D014982:Xenopus laevis
chemical_list: D004277:DNA, Single-Stranded; D005656:Fungal Proteins; D004247:DNA; D004265:DNA Helicases