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个人简介

Following my DPhil studies at the University of Oxford, on DNA repair during plant seed dormancy, I spent three years at the Institut pour la Recherché sur le Cancer in Villejuif, France working on mammalian DNA ligases. This work was very successful and we were the first to describe a novel form of the enzyme, which is now called DNA ligase III. I then spent two years in the Biochemistry Department at Michigan State University in East Lansing, USA, working on the mitochondrial DNA polymerase from the fruit fly Drosophila melanogaster. On returning to the UK, I worked at the Paterson Institute for Cancer Research in Manchester and spent the next 16 years there, studying DNA repair mechanisms and how they can both help to prevent the development of cancer and also act to decrease the effectiveness of certain chemotherapeutic drugs.I then moved to the University of Manchester for two years before arriving at the University of Salford at the start of 2008.

研究领域

My current research interests focus on a group of enzymes involved in DNA repair. It is estimated that the genomic DNA in each cell is subjected to 10,000 DNA damaging events each day. To combat this damage and to ensure genetic stability, cells have evolved several different DNA repair mechanisms; one of these is base excision repair (BER). DNA glycosylases are enzymes that remove damaged (chemically altered) bases from DNA in the first step of BER. Mammalian cells have several families of DNA glycosylases to protect them from different types of DNA damage. My work, and that of others, has shown that there is redundancy in the system; different DNA glycosylases can recognize similar types of damaged bases. I am particularly interested in a family of DNA glycosylases called Nei-Like (NEIL) that were first discovered in 2002. The third member of this family, NEIL3, is particularly interesting as it only exists in vertebrates, shows a limited pattern of gene expression (including overexpression in metastatic cancer cells) and contains structural differences to the other family members. Therefore, my work is focused on determining the biological role of this DNA glycosylase using molecular and cell biology techniques in collaboration with colleagues in Manchester and Liverpool.

近期论文

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Cooley, N & Elder, R & Povey, A (2010) 'The effect of Msh2 knockdown on methylating agent induced toxicity in DNA glycosylase deficient cells', Toxicology, 268, pp.111-117. Pachkowski, B & Tano, K & Afonin, V & Elder, R & Takeda, S & Watanabe, M & Swenberg, J & Nakamura, J (2009) 'Cells deficient in PARP-1 show an accelerated accumulation of DNA single strand breaks, but not AP sites, over the PARP-1-proficient cells exposed to MMS.', Mutation Research, 671, pp.93-99. Parsons, J & Elder, R (2003) 'DNA N-glycosylase deficient mice: a tale of redundancy', Mutation Research, 531(1-2), pp.165-175 Elder, R & Dianov, G (2002) 'Repair of dihydrouracil supported by base excision repair in mNTH1 knock-out cell extracts.', J Biol Chem, 277(52), pp.50487-50490.

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