Author
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DEPAMPHILIS, MELVIN - NATIONAL INST. HEALTH |
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Li, Congjun - Cj |
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Submitted to: Encyclopedia of Biological Chemistry
Publication Type: Review Article Publication Acceptance Date: 2/18/2004 Publication Date: 9/1/2004 Citation: DePamphilis, M.L., Li, C. 2004. DNA replication: eukaryotic origins and the origin recognition complex. Encyclopedia of Biological Chemistry (W.J. Lennarz & M.D. Lane, eds), Elsevier, Oxford. vol. 1:753-760. Interpretive Summary: This article is to review our current knowledge of DNA replication, a basic step of cell growth and proliferation. Eukaryotic origins of DNA replication and the proteins that recognize them constitute the premier step in determining where and when DNA replication begins. Replication origins are defined either as genetically required sequences that bind initiation proteins (the "replicator"), or as specific sites where DNA replication begins. So far, both the replicator and the initiation site reside at the same locus ("replication origin") in all bacteria, bacterial plasmids, bacteriophage, viruses, yeast, protozoa, and mitochondria genomes examined so far. Based on analyses of yeast, flies, frogs and mammals, a simple, universal picture of DNA replication origins in eukaryotic chromosomes has emerged. They consist of one or more binding sites for a unique six subunit protein complex called the "origin recognition complex" (ORC), and an easily unwound DNA sequence called the "DNA unwinding element" (DUE) where replication begins. In addition, the sites where initiation of DNA replication occur, particularly in multicellular organisms such as frogs, flies and mammals, are determined both by genetic and epigenetic factors, thus introducing a degree of flexibility this allows metazoan genomes to change their pattern of replication origins to accommodate changes in the length of S-phase and in the pattern of gene expression. This ability to be flexible allows evolution to retain the same basic mechanism for DNA replication in all eukaryotes without interfering with the creation of more complex organisms. Technical Abstract: Eukaryotic origins of DNA replication and the proteins that recognize them constitute the premier step in determining where and when DNA replication begins. Replication origins are defined either as genetically required sequences that bind initiation proteins (the "replicator"), or as specific sites where DNA replication begins. So far, both the replicator and the initiation site reside at the same locus ("replication origin") in all bacteria, bacterial plasmids, bacteriophage, viruses, yeast, protozoa, and mitochondria genomes examined so far. Based on analyses of yeast, flies, frogs and mammals, a simple, universal picture of DNA replication origins in eukaryotic chromosomes has emerged. They consist of one or more binding sites for a unique six subunit protein complex called the "origin recognition complex" (ORC), and an easily unwound DNA sequence called the "DNA unwinding element" (DUE) where replication begins. In addition, the sites where initiation of DNA replication occur, particularly in multicellular organisms such as frogs, flies and mammals, are determined both by genetic and epigenetic factors, thus introducing a degree of flexibility this allows metazoan genomes to change their pattern of replication origins to accommodate changes in the length of S-phase and in the pattern of gene expression. This ability to be flexible allows evolution to retain the same basic mechanism for DNA replication in all eukaryotes without interfering with the creation of more complex organisms. |
