Highlights of research His PhD work was instrumental in the identification of a DNA damage inducible protein, known as Protein X, as RecA protein, which plays a key role in DNA recombination and repair. He then moved to
Yale University to work with Paul Howard-Flanders, where he purified and characterised RecA protein. There, he discovered many key aspects relating to the way that cells mediate the DNA-DNA interactions and strand exchanges required for the recombinational repair of DNA damage. Parallel studies were carried out in the groups of Charles Radding (also at Yale University) and Robert Lehman (
Stanford University). These three laboratories provided the groundwork for our current understanding of the enzymatic mechanisms of recombination. After moving to the UK in 1985, West continued his work in bacterial systems, and set about trying to identify cellular proteins capable of resolving recombination intermediates. He identified
RuvC as the first cellular enzyme that resolves recombination intermediates and characterised how this nuclease cuts
Holliday junctions. He was also the first to show that RuvA and RuvB are motor proteins that mediate Holliday junction branch migration. His biochemical studies were compounded by genetic work from the laboratory of Robert Lloyd (
University of Nottingham). West’s laboratory then moved into
eukaryotic systems, where he discovered eukaryotic Holliday junction resolvases (yeast Yen1 and human GEN1). The identification of GEN1 was the culmination of 18 years of research, and opened up the field to allow a genetic analysis of the pathways by which recombination intermediates are processed. Present understanding indicates that there are three distinct pathways of Holliday junction processing in human cells involving BLM-topoIIIα-RMI1-RMI2 (BTR), SLX1-SLX4-MUS81-EME1-ERCC1-XPF (SMX) and GEN1. His laboratory discovered that the Holliday junction resolvase activities of MUS81 and GEN1 are regulated so that they act late in the cell cycle to ensure chromosome segregation. In addition to the discovery of cellular Holliday junction resolvases, West was the first to purify human RAD51 protein (the eukaryotic ortholog of RecA), and to show that it promotes homologous pairing and strand exchange reactions similar to those mediated by RecA. In addition, he purified and then visualised the BRCA2 breast cancer tumour suppressor, showing that it acts as a molecular chaperone for the association RAD51 with DNA. His laboratory also discovered that
Aprataxin, which is defective in a progressive neurological disorder known as
Oculomotor apraxia, is a 5'-deadenylase that removes AMP from 5'-termini following abortive DNA ligation. Recently his laboratory determined the high resolution structure of the two RAD51 paralog complexes (made up of RAD51B, RAD51C, RAD51D, XRCC2 and XRCC3) using
cryo-electron microscopy and, in work considered to be a tour-de-force in the field, he defined their functions in DNA repair and tumour avoidance. He also used cryo-EM and biochemistry to determine the mechanism of single strand DNA annealing by the RAD52 protein. Due to the role that DNA repair plays in the maintenance of genome stability and cancer avoidance, West’s work contributes to the understanding the molecular basis of human disease. In particular his laboratory discovered that loss of a nucleotide pool scavenger known as DNPH1 sensitizes cancer cells to the PARP inhibitor
olaparib, a drug that is currently in clinical use for the treatment of breast, ovarian and prostate cancers caused by inheritable mutations in
BRCA1 or
BRCA2. He is an international speaker, and gives several keynote lectures each year as a communicator of the intricacies of DNA recombination and repair.
Other professional activities West has been on the editorial boards of a number of journals including
e-Life (2014-2016),
EMBO Journal (1996-2020) and
EMBO Reports (2000-2022). He is currently on the editorial board of DNA Repair. Steve is Chair of the International Advisory Board of the Chinese Institutes for Medical Research in
Beijing, China. Previously, he was a member of the Scientific Advisory Board of the
Leibniz Institute on Aging, Fritz Lippman Institute, Jena, Germany, the Center for Chromosome Instability,
University of Copenhagen, Denmark, the
China Medical University (Taiwan), the Guangdong Key Laboratory of Genome Stability in Shenzhen, China, and the
Max Planck Institute for Biochemistry, Martinsreid, Germany. Steve serves on the Council of the
Royal Society. He is a serial conference organiser, having organised (or co-organised) more than 30 conferences throughout his career. For many years he has organised the biennial International Conference on ‘Mechanisms of Recombination’. The next meeting in the series will take place in Europe in May 2027 and is supported by Fusion. ==Honours and awards==