Steve Jackson PhD FRS FMedSci, Frederick James Quick Professor of Biology, Member of the Biochemistry Department. Steve is also an Associate Faculty Member of the Wellcome Trust Sanger Institute.
Maintenance of genome stability
Can we alleviate disease by targeting DNA repair? The DNA in our cells constantly receives insults from natural radiation, sunlight, chemicals and cell metabolism, leading to DNA breaks and potential disruption of genome integrity and gene expression. Cell survival and genome integrity are supported by a series of events, the DNA- damage response (DDR), which detect, signal the presence of, and then mediate DNA repair. Defects in the DDR are associated with a wide variety of conditions including developmental disorders, immunodeficiencies, infertility, premature ageing and cancer.
Our research continues to characterise the cell biology of DDR pathways to discover new therapeutic strategies, using yeast and mammalian cells in culture. We aim to identify important DDR proteins, and their functions, regulation and roles in diverse cellular events.
For example, we recently developed a new screening technique to find enzymes that modify DDR protein activity, focusing on the many cellular proteins involved in ubiquitylation/deubiquitylation. We are also exploring the concepts of synthetic lethality and synthetic viability to identify novel therapeutic targets for a range of human diseases.
• Xi W et al.(2016) Molecular Insights into Division of Single Human Cancer Cells in On-Chip Transparent Microtubes. ACS Nano 2016 Jun 15. [Epub ahead of print]
• Chiang TW et al.(2016) CRISPR-Cas9(D10A) nickase-based genotypic and phenotypic screening to enhance genome editing. Sci Rep 6:24356.
• Schmidt CK et al. (2015) Systematic E2 screening reveals a UBE2D-RNF138-CtIP axis promoting DNA repair. Nat Cell Biol 17(11):1458-70
• Wijnhoven P et al. (2015) USP4 Auto-Deubiquitylation Promotes Homologous Recombination. Mol Cell 60(3):362-73.
• Forment JV et al. (2015) When two is not enough: a CtIP tetramer is required for DNA repair by Homologous Recombination. Nucleus 6(5):344-8.
• Forment JV and Jackson SP (2015) A flow cytometry-based method to simplify the analysis and quantification of protein association to chromatin in mammalian cells. Nat Protoc 10(9):1297-307.
• Brown JS et al. (2015) Neddylation promotes ubiquitylation and release of Ku from DNA-damage sites. Cell Rep 11(5):704-14.