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© The Rockefeller University Press, 0021-9525/2003/2/287 $5.00
The Journal of Cell Biology, Volume 160, Number 3, 287-287

Replicating dominos

Early (green) and later (red) replication foci are next to each other. Cardoso/Elsevier

The choreography of DNA replication has been a mysterious black box. How is replication targeted to different, reproducibly localized DNA domains at the early, middle, and late stages of S phase? Rather than invoking a homunculus, Anje Sporbert, Cristina Cardoso (Max Delbrück Center for Molecular Medicine, Berlin, Germany), and colleagues have come up with a domino model that runs itself once the replication program gets started.

Cardoso's group focused on the dynamics of PCNA, a sliding clamp that aids in DNA polymerase processivity. Recovery of fluorescence after bleaching of PCNA was slow, suggesting that PCNA from within a given replication focus is recycled to load at each new Okazaki fragment.

But the picture over the longer term is very different. Based on pulse labeling of DNA replication and PCNA, bulk PCNA is released from the sites that were replicated earlier and keeps up with the sites of ongoing replication. The recycling at this timescale is indirect—it is unbleached PCNA from the nucleoplasm that assembles at the new replication foci. Importantly, these foci are found preferentially right next to the recently bleached foci.

Earlier workers mapping DNA replication sites had noted, but had not dwelt upon, this close apposition of sequential replication foci. Cardoso believes that the pattern is crucial. "We think the major DNA replication program could be explained by this," she says. Activity at early replication foci may transmit a signal down the DNA strand to activate neighboring foci, either by pulling physically on the DNA (like undoing a shoelace) or by an unknown chromatin-modifying mechanism. "The program would be fixed," says Cardoso, "as long as the first sites to fire were fixed."

Reference:

Sporbert, A., et al. 2002. Mol. Cell. 10:1355–1365.[CrossRef][Medline]

William A. Wells

wellsw{at}rockefeller.edu

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This Article Full Text (PDF, 581K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wells, W. A. Search for Related Content PubMed Articles by Wells, W. A. Social Bookmarking                            What's this?