On the road to replication

  • Diffley J
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Abstract

EMBO Mol Med (2016) 8: 77–79OpenUrlFREE Full TextI had left New York a few days earlier—Halloween 1990—to start my new research group at the ICRF Clare Hall laboratories. It was Guy Fawkes Night at Clare Hall, which is located in the rural village of South Mimms just north of London. Guy Fawkes was a 17th century religious zealot who tried unsuccessfully to blow up the Houses of Parliament; he was captured, tortured, and executed, events which are celebrated in Britain every November 5th with fireworks and bonfires. I was standing in a soggy field, feet soaking wet and freezing in the drizzling rain, eating a cold sausage, and watching my new colleagues burn an effigy of our laboratory manager, Frank Fitzjohn, on the bonfire. I had clearly arrived in a foreign land!At the time of my hiring, I was given the choice of the Clare Hall laboratories or the Lincoln's Inn Fields laboratories in central London. With LIF's reputation for cutting‐edge cancer research, and having lived in another big city, New York, for most of my life, friends and colleagues had expected me to choose LIF. Clare Hall was not yet the internationally recognised powerhouse of genome stability research it later became, but it was clear to me that I had found a home amongst a group of outstanding young biochemists including Rick Wood and Steve West. Soon Tim Hunt, Julian Blow, and Noel Lowndes joined the faculty, generating a vibrant atmosphere for cell cycle research. And, under the direction of Tomas Lindahl, the future of Clare Hall seemed very bright.I had come to Clare Hall straight from a postdoc in Bruce Stillman's laboratory at Cold Spring Harbor. When I first arrived in Bruce's laboratory, he had just embarked on a major project to dissect cell …

Figures

  • 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. 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 Dbf4dependent 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.

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CITATION STYLE

APA

Diffley, J. F. (2016). On the road to replication. EMBO Molecular Medicine, 8(2), 77–79. https://doi.org/10.15252/emmm.201505965

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