Journal
BIOESSAYS
Volume 25, Issue 12, Pages 1158-1167Publisher
WILEY-BLACKWELL
DOI: 10.1002/bies.10370
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Funding
- NATIONAL CANCER INSTITUTE [P01CA013106] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM045436] Funding Source: NIH RePORTER
- NCI NIH HHS [P01 CA013106, CA13106] Funding Source: Medline
- NIGMS NIH HHS [R01 GM045436] Funding Source: Medline
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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. (C) 2003 Wiley Periodicals, Inc.
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