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Professor Steve Jackson FRS FMedSci Maintenance of genome stability Steve is the Frederick James Quick Professor of Biology, and member of the Biochemistry Department. Steve is also an Associate Faculty Member of the Wellcome Trust Sanger Institute. |
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Our work focuses on the DNA-damage response (DDR): the set of events that optimises cell survival and genomic integrity by detecting DNA damage, signalling its presence and mediating its repair.The importance of the DDR is underscored by defects in it being associated with various pathologies, including neurodegenerative disease, immunodeficiency, developmental defects, premature ageing, infertility and cancer. Indeed, we recently identified mutations in the DDR protein CtIP that cause Seckel syndrome, a recessively inherited dwarfism disorder characterised by microcephaly, and a related disease called Jawad syndrome (1). For many years, we have been studying how protein phosphorylation controls the DDR.We have now carried out phospho-proteomic screens in collaboration with Dr. Chunaram Choudhary (Copenhagen, Denmark), enabling us to identify novel substrates of the cell-cycle checkpoint kinase Chk1 (2). In addition, we identified a DNA-damage dependent phosphorylation site on the key homologous recombination protein Rad51 that controls Rad51 function (3). Furthermore, we have studied how DNA damage arises in the absence of Chk1 activity, showing that this is mediated by the endonuclease Mus81/Eme1 (4). Another recent highlight has been our data showing how DNA replication stress leads to the formation of chromosomal fragile sites in G1 phase of the next cell cycle (5).This work has thus helped our understanding of how fragile sites arise and contribute to cancer and other diseases. In addition, our studies have led to new therapeutic opportunities.To exploit these, with the assistance of Cancer Research Technology and Cambridge University, Steve Jackson founded MISSION Therapeutics whose aim is to translate new molecular understandings of human cell biology into drugs that will markedly improve the management of life-threatening diseases, particularly cancer.
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Plain English: Selected publications: • Qvist P, Huertas P, Jimeno S, Nyegaard M, Hassan MJ, Jackson SP and Børglum AD (2011) CtIP mutations cause Seckel and Jawad syndromes. PLoS Genetics 7, e1002310 (1) • Blasius M, Forment JV,Thakkar N,Wagner SA, Choudhary C and Jackson SP (2011) A phospho- proteomic screen identifies substrates of the checkpoint kinase Chk1. Genome Biol 12(8), R78 (2) • Flott S, Kwon Y, Pigli YZ, Rice PA, Sung P and Jackson SP (2011) Regulation of Rad51 function by phosphorylation. EMBO Rep 12, 833-9 (3) • Forment JV, Blasius M, Guerini I and Jackson SP (2011) Structure-Specific DNA Endonuclease Mus81/Eme1 Generates DNA Damage Caused by Chk1 Inactivation. PLoS ONE 6, e23517 (4) • Harrigan JA, Belotserkovskaya R, Coates J, Dimitrova DS, Polo SE, Bradshaw CR, Fraser P and Jackson SP (2011) Replication stress induces 53BP1-containing OPT domains in G1 cells. J Cell Biol 193, 97-108 (5)
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Page updated: 11 May 2012 by mjl76 The Wellcome Trust/Cancer Research UK Gurdon Institute, |
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