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Molecular and Cellular Biology, September 2008, p. 5265-5274, Vol. 28, No. 17
0270-7306/08/$08.00+0     doi:10.1128/MCB.00181-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

In Xenopus Egg Extracts, DNA Replication Initiates Preferentially at or near Asymmetric AT Sequences ^,

Slavica Stanojcic, Jean-Marc Lemaitre, Konstantin Brodolin, Etienne Danis, and Marcel Mechali^*

Institute of Human Genetics, CNRS, 34396 Montpellier Cedex 5, France

Received 4 February 2008/ Returned for modification 28 February 2008/ Accepted 10 June 2008

Previous observations led to the conclusion that in Xenopus eggs and during early development, DNA replication initiates at regular intervals but with no apparent sequence specificity. Conversely, here, we present evidence for site-specific DNA replication origins in Xenopus egg extracts. Using DNA, we show that DNA replication origins are activated in clusters in regions that contain closely spaced adenine or thymine asymmetric tracks used as preferential initiation sites. In agreement with these data, AT-rich asymmetric sequences added as competitors preferentially recruit origin recognition complexes and inhibit sperm chromatin replication by increasing interorigin spacing. We also show that the assembly of a transcription complex favors origin activity at the corresponding site without necessarily eliminating the other origins. Thus, although Xenopus eggs have the ability to replicate any kind of DNA, AT-rich domains or transcription factors favor the selection of DNA replication origins without increasing the overall efficiency of DNA synthesis. These results suggest that asymmetric AT-rich regions might be default elements that favor the selection of a DNA replication origin in a transcriptionally silent complex, whereas other epigenetic elements linked to the organization of domains for transcription may have further evolved over this basal layer of regulation.

Published ahead of print on 23 June 2008.

Supplemental material for this article may be found at http://mcb.asm.org/.

Present address: Institute of Functional Genomics, INSERM, Genome Plasticity and Cellular Aging, 141 Rue de la Cardonille, 34396 Montpellier Cedex 5, France.