Abstract
The initiation of DNA replication in eukaryotic cells is tightly controlled to ensure that the genome is faithfully duplicated once each cell cycle. Genetic and biochemical studies in several model systems indicate that initiation is mediated by a common set of proteins, present in all eukaryotic species, and that the activities of these proteins are regulated during the cell cycle by specific protein kinases. Here we review the properties of the initiation proteins, their interactions with each other, and with origins of DNA replication. We also describe recent advances in understanding how the regulatory protein kinases control the progress of the initiation reaction. Finally, we describe the checkpoint mechanisms that function to preserve the integrity of the genome when the normal course of genome duplication is perturbed by factors that damage the DNA or inhibit DNA synthesis.
MeSH terms
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Animals
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Carrier Proteins / metabolism
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Cell Cycle Proteins / metabolism
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Chromosomes / metabolism*
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Cyclin-Dependent Kinases / metabolism
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DNA Damage
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DNA Replication / physiology*
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DNA-Binding Proteins / metabolism
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Humans
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In Vitro Techniques
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Nuclear Proteins / metabolism
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Origin Recognition Complex
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Protein Serine-Threonine Kinases / metabolism
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Replication Origin
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S Phase
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae Proteins*
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Schizosaccharomyces / genetics
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Schizosaccharomyces / metabolism
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Schizosaccharomyces pombe Proteins*
Substances
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CDC45 protein, S cerevisiae
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CDC6 protein, S cerevisiae
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Carrier Proteins
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Cell Cycle Proteins
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DNA-Binding Proteins
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Nuclear Proteins
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Origin Recognition Complex
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Saccharomyces cerevisiae Proteins
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Schizosaccharomyces pombe Proteins
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cdc18 protein, S pombe
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CDC7 protein, S cerevisiae
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CDC7 protein, human
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cdc7 protein, S pombe
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Protein Serine-Threonine Kinases
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Cyclin-Dependent Kinases