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Research Project: Endocrine and Immune Mechanisms Affecting Growth in Young Cattle

Location: Growth Biology Laboratory

Title: Chromosome Replication: Eukaryotic DNA Replication Origins and the Origin Recognition Complex

Authors
item Depamphilis, Melvin - NATIONAL INST. HEALTH
item Li, Congjun

Submitted to: Encyclopedia Of Biological Chemistry
Publication Acceptance Date: February 18, 2004
Publication Date: September 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, Pp 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.

 
Project Team
Elsasser, Theodore
Li, Congjun

Publications

Related National Programs
  Food Animal Production (101)

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   Estrogen Progesterone Modulation of Nitric Oxide Production in Endotoxemic Calves

 
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