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Review
. 2004 Jul;5(7):686-91.
doi: 10.1038/sj.embor.7400185.

The Replicon Revisited: An Old Model Learns New Tricks in Metazoan Chromosomes

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Free PMC article
Review

The Replicon Revisited: An Old Model Learns New Tricks in Metazoan Chromosomes

Mirit I Aladjem et al. EMBO Rep. .
Free PMC article

Abstract

The origins of DNA replication were proposed in the replicon model to be specified genetically by replicator elements that coordinate the initiation of DNA synthesis with gene expression and cell growth. Recent studies have identified DNA sequences in mammalian cells that fulfil the genetic criteria for replicators and are beginning to uncover the sequence requirements for the initiation of DNA replication. Mammalian replicators are com- posed of non-redundant modules that cooperate to direct initiation to specific chromosomal sites. Conversely, replicators do not show strong sequence similarity, and their ability to initiate replication depends on the chromosomal context and epigenetic factors, as well as their primary sequence. Here, we review the properties of metazoan replicators, and discuss the genetic and epigenetic factors that determine where and when DNA replication is initiated.

Figures

Figure 1
Figure 1
The replicon model. A trans-acting protein encoded by the initiator gene was proposed to recognize a cis-acting sequence (the replicator) that controls the initiation of DNA replication in the replicon (Jacob et al, 1963).
Figure 2
Figure 2
Sequence features of metazoan replicators that are active at ectopic chromosomal sites. The genes surrounding the six replicators in five native loci are shown in blue (not to scale), and the elements required for initiation in the native locus are shown as hatched blue boxes. Mapped initiation regions in each replicator are indicated by purple triangles. In each ectopic replicator (yellow), the sequence elements in red have been shown to be required for full initiation activity. AG, asymmetric purine:pyrimidine regions; AT, AT-rich element; BEND, a sequence-directed bent DNA region; DHFR, dihydrofolate reductase; DNR, dinucleotide repeat; CpG, CpG island; LamB, lamin B; LCR, locus-control region; RIP60, replication-initiation region protein 60 kDa.
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