Stephen C. West
The Francis Crick Institute
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Primary Section: 21, Biochemistry Membership Type:
International Member
(elected 2016)
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Biosketch
Steve West leads the DNA Recombination and Repair Laboratory at the Francis Crick Institute. He gained his BSc and PhD at Newcastle University, and was a post-doctoral associate at Yale University. His research interests lie in the mechanisms of genetic recombination and DNA repair, with an emphasis on how they relate to human disease. Following his studies with the RecA and RAD51 recombinases, he identified enzymes from bacteria, yeast and humans that resolve DNA recombination intermediates known as Holliday junctions. These nucleases play a critical role in ensuring the breakage of covalent sister chromatid linkages prior to chromosome segregation at mitosis. Steve is a Fellow of the Royal Society, the Academy of Medical Sciences, Foreign Associate of the National Academy of Sciences USA, and International Honorary Member of the American Academy of Arts and Sciences.
Research Interests
Steve West was trained as a biochemist and discovered the cellular enzymes that resolve recombination intermediates (Holliday junctions) to allow chromosome segregation at mitosis. In bacteria, resolution is mediated by the RuvC protein, together with the associated RuvAB proteins that promote the branch migration of Holliday junctions. In human cells, resolution requires GEN1 and the SMX trinuclease complex. He was the first to purify human RAD51 and to show that the BRCA2 tumour suppressor targets RAD51 to single stranded DNA. Although his primary work is in the area of recombinational repair, he also discovered that Aprataxin, which is defective in a progressive neurological disorder known as Oculomotor Apraxia, is a deadenylase that removes AMP from 5'-termini following abortive DNA ligation. In recent work, his laboratory demonstrated that inhibition of the nucleotide scavenger DNPH1 sensitises BRCA-deficient tumour cells to PARP inhibitors, potentially offering new routes to therapy.
