Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Feb 1;8(2):77-9.
doi: 10.15252/emmm.201505965.

On the road to replication

John F X Diffley  1
Affiliations

On the road to replication

John F X Diffley. EMBO Mol Med. .

Abstract

The 2016 Louis‐Jeantet Prize for Medicine winner John Diffley tells the story of his path to characterise and understand DNA replication.

PubMed Disclaimer

Figures

Figure 1
Figure 1. DNA replication bubbles from Drosophila cleavage nuclei
This figure, reproduced with permission from Kriegstein and Hogness (1974), shows an electron micrograph (and accompanying trace) of DNA purified from very early (< 1 h) fertilised Drosophila melanogaster embryos. This particular molecule shows 23 replication bubbles in a region of 119 kb.
Figure 2
Figure 2. A model for DNA replication
This model summarises some of our current understanding of how DNA replication initiates. In the first step, which is inhibited by CDK, ORC, Cdc6, and Cdt1 load the MCM helicase and an inactive double hexamer bound around double‐stranded DNA. In the second step, which is promoted by CDK, the listed firing factors, including the Dbf4‐dependent kinase, contribute to activating MCM by generating the Cdc4‐MCM‐GINS (CMG) holo‐helicase. This is followed by assembly of the complete replisome—the enzymes and other proteins that copy the genome. The DNA damage checkpoint kinase Rad53, when active, inhibits origin firing and stabilises stalled replication forks. Additional detail is found in the text.
See this image and copyright information in PMC

References

    1. Bell SP, Stillman B (1992) ATP‐dependent recognition of eukaryotic origins of DNA replication by a multiprotein complex. Nature 357: 128–134 - PubMed
    1. Dahmann C, Diffley JFX, Nasmyth KA (1995) S‐phase‐promoting cyclin‐dependent kinases prevent re‐replication by inhibiting the transition of replication origins to a pre‐replicative state. Curr Biol 5: 1257–1269 - PubMed
    1. Diffley JFX, Cocker JH (1992) Protein‐DNA interactions at a yeast replication origin. Nature 357: 169–172 - PubMed
    1. Diffley JFX, Cocker JH, Dowell SJ, Rowley A (1994) Two steps in the assembly of complexes at yeast replication origins in vivo . Cell 78: 303–316 - PubMed
    1. Kriegstein HJ, Hogness DS (1974) Mechanism of DNA replication in Drosophila chromosomes: structure of replication forks and evidence for bidirectionality. Proc Natl Acad Sci USA 71: 135–139 - PMC - PubMed

Publication types

MeSH terms

Substances