Cancer Research UK

Our other websites:

London Research Institute

Stephen West : Genetic Recombination

Goals

Our genetic material (DNA) is continually subjected to damage, either from endogenous sources such as reactive oxygen species produced as by-products of oxidative metabolism, from the breakdown of replication forks during cell growth, or by agents in the environment such as ionising radiation or carcinogenic chemicals. To cope with such damage, cells employ a variety of repair processes that are specialised to recognise different types of lesions in DNA. These repair systems are essential for the maintenance of genome integrity and for cancer avoidance. The focus of our research is to determine the cellular mechanisms for repair and, most importantly, to define the cellular defects that lead to cancers and neurodegeneration, two common consequences of defective damage processing. Our present work focuses on the molecular analysis of proteins such as BRCA2, GEN1, MUS81-EME1, SLX1-SLX4, FANCM and SEN1.

Selected Papers

Matos J, Blanco MG, Maslen SL, Skehel JM, West SC. Regulatory control of the resolution of DNA recombination intermediates during meiosis and mitosis. Cell. 2011;147:158-172 (Abstract)
Wechsler T, Newman S, West SC. Aberrant chromosome morphology in human cells defective for Holliday junction resolution. Nature. 2011;471:642-646 (Abstract)
Rass U, Compton SA, Matos J, Singleton MR, Ip SC, Blanco MG, Griffith JD, West SC. Mechanism of Holliday junction resolution by the human GEN1 protein. Genes Dev. 2010;24:1559-1569 (Abstract)
Thorslund T, McIlwraith MJ, Compton SA, Lekomtsev S, Petronczki M, Griffith JD, West SC. The breast cancer tumor suppressor BRCA2 promotes the specific targeting of RAD51 to single-stranded DNA. Nat. Struct. Mol. Biol. 2010;17:1263-1265 (Abstract)
Deans AJ, West SC. FANCM connects the genome instability disorders Bloom’s Syndrome and Fanconi Anemia. Mol. Cell. 2009;36:943-953 (Abstract)
Ahel I, Ahel D, Matsusaka T, Clark AJ, Pines J, Boulton SJ, West SC. Poly(ADP-ribose)-binding zinc finger motif in DNA repair/checkpoint proteins. Nature. 2008;451:81-85 (Abstract)
Ip SC, Rass U, Blanco MG, Flynn HR, Skehel JM, West SC. Identification of Holliday junction resolvases from humans and yeast. Nature. 2008;456:357-361 (Abstract)
Ahel I, Rass U, El-Khamisy SF, Katyal S, Clements PM, McKinnon PJ, Caldecott KW, West SC. The neurodegenerative disease protein aprataxin resolves abortive DNA ligation intermediates. Nature. 2006;443:713-716 (Abstract)
Esashi F, Christ N, Gannon J, Liu Y, Hunt T, Jasin M, West SC. CDK-dependent phosphorylation of BRCA2 as a regulatory mechanism for recombinational repair. Nature. 2005;434:598-604 (Abstract)