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DNA replication origins: from sequence specificity to epigenetics

Nature Reviews Genetics volume 2, pages 640–645 (2001)Cite this article

Abstract

Site-specific initiation of DNA replication is a conserved function in all organisms. In Escherichia coli and Saccharomyces cerevisiae, DNA replication origins are sequence specific, but in multicellular organisms, origins are not so clearly defined. In this article, I present a model of origin specification by epigenetic mechanisms that allows the establishment of stable chromatin domains, which are characterized by autonomous replication. According to this model, origins of DNA replication help to establish domains of gene expression for the generation of cell diversity.

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Figure 1: Specificity of initiation of DNA replication from bacteria to metazoans.
Figure 2: Main features of the β-globin and DHFR initiation regions of DNA replication.
Figure 3: From a single bacterial replicon to multiple metazoan replicons.

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Acknowledgements

I wish to thank D. Fisher, D. Maiorano and P. Françon for helpful comments on this manuscript. Work in our laboratory is mainly supported by the CNRS, ARC and FRM.

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Authors and Affiliations

  1. Institute of Human Genetics, CNRS, Genome Dynamics and Development, 141 rue de la Cardonille, Montpellier, 34396, France

    Marcel Méchali

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  1. Marcel Méchali
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DATABASE LINKS

β-globin

DHFR

Myc

HML

HMR

orc1

orc2

orc5

Sir1

Gal4

Sir3

HP1

Orc2

Orc4

IgH

ARS1

BAH

PCNA

CAF1

Glossary

(A+T)-HOOK MOTIF

A nine-amino-acid protein domain that binds to the minor groove of (A+T)-rich DNA.

BOUNDARY ELEMENT

A DNA element that lies between two gene-controlling elements, such as a promoter and enhancer, preventing their communication or interaction. The function of boundary elements is usually mediated by the binding of specific factors.

BROMO-ADJACENT-HOMOLOGY DOMAIN

A domain of unknown function that is found in several proteins that are involved in chromatin remodelling and epigenetic mechanisms.

CHROMODOMAIN

A protein motif that is involved in binding certain methylated histones; often associated with transcriptional repression.

HETEROCHROMATIN

The densely staining regions of the nucleus that generally contain condensed, transcriptionally inactive regions of the genome.

HIGH MOBILITY GROUP PROTEINS

Non-histone proteins involved in chromatin structure and gene regulation.

INSULATOR ELEMENT

A chromatin element that acts as a barrier against the influence of positive (enhancers) or negative (silencers) signals.

ORIGIN RECOGNITION COMPLEX

A complex of six subunits that binds to the origins of DNA replication in an ATP-dependent manner.

POLYCOMB-GROUP PROTEINS

Genes that are involved in the heritable repression of developmentally regulated genes, such as the homeotic genes.

POSITION-EFFECT VARIEGATION

A phenomenon discovered in Drosophila, which occurs when genes placed close to large heterochromatic regions are repressed. This repression is metastable, in that the silenced state can be occasionally released, giving rise to derepressed cells and a variegated phenotype.

REPLICON

A genetic element that contains a single origin of DNA replication, recognized by a specific positive regulatory protein or complex.

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Méchali, M. DNA replication origins: from sequence specificity to epigenetics. Nat Rev Genet 2, 640–645 (2001). https://doi.org/10.1038/35084598

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