John Diffley is a biochemist recognized for his work on eukaryotic DNA replication. He is especially known for his work on the mechanism and regulation of replication initiation. Diffley was born and raised in the New York City area. He obtained his B.A., M.S. and Ph.D. from New York University. He was a postdoctoral fellow at Cold Spring Harbor from 1984-1990 before moving to the Clare Hall Laboratories, Imperial Cancer Research Fund in 1990 as a Junior Group Leader. He became Director of the Clare Hall Laboratories and Deputy Director of the London Research Institute (Cancer Research UK) in 2006. He is now Associate Research Director of the Francis Crick Institute. He is a member of the European Molecular Biology Organization (EMBO), a Fellow of the Academy of Medical Sciences, a Fellow of the Royal Society and a member of the National Academy of Sciences. He has won the Paul Marks Prize for Cancer Research, the Louis Jeantet Prize for Medicine and the Canada Gairdner International Award.

Research Interests

Diffley's laboratory uses biochemistry, genetics and cell biology to understand how eukaryotic cells replicate their chromosomes, thus ensuring stable maintenance of their genomes. His work has shown in molecular detail how DNA replication origins are regulated to ensure once per cell cycle replication. With his reconstitution of the entire chromatin replication pathway using purified proteins, he has developed approaches to understand how the replicative DNA helicase is loaded at origins, how it is activated, how it nucleates assembly of the replication machinery and how the replication machinery displaces and re-deposits nucleosomes during replication. He has also shown that DNA damage checkpoints regulate DNA replication on damaged DNA templates by inhibiting replication origin firing and promoting replication fork stability. His work has shown how loss of checkpoints or misregulation of normal cell cycle control can cause genome instability by interfering with normal DNA replication, which has important implications forcancer biology.

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Section 21: Biochemistry