Williams, David M. - University of Sheffield

个人简介

Dr. Williams obtained a BSc in Chemistry from the University of Liverpool in 1985, which was followed by a PhD from the same institution in 1988. From 1988, he was a Postdoctoral Research Fellow at the Max-Planck Institute for Experimental Medicine in Göttingen and from 1992-1995 at the MRC Laboratory of Molecular Biology in Cambridge. In 1995 he became a demonstrator at the University of Sheffield. In 1999 he became a lecturer and in 2006 a senior lecturer. In 2014 he was promoted to Reader.

研究领域

Our main areas of research are in the synthesis of modified nucleosides and nucleotides and their applications. Currently we are interested in the chemical synthesis of 5'-triphosphates of base-modified, nucleoside analogues that have altered base pairing specificities. We are studying the incorporation of these analogues into DNA by polymerase enzymes in order to gain an insight into the role of base pairing during DNA replication and DNA mutagenesis. Exposure to alkylating agents can lead to the formation of highly toxic O6-alkylguanine lesions within DNA. We have developed chemical methodology for the preparation of oligodeoxyribonucleotides containing a variety of O6-alkylguanine analogues and these are being used to study DNA recognition and repair by the human protein O6-methylguanine-DNA methyltransferase (MGMT) and the alkyltransferase-like protein Atl1. Other areas of interest include the use SELEX for the design of nucleic acid-based ligands and catalysts containing chemically synthesised imidazolyl and amino modified nucleotides of dUTP and 7-deazadATP, studying the structural properties of nucleic acids containing modified pyrimidine and purine bases and the design and synthesis of modified oligodeoxyribonucleotides for DNA-DNA and DNA-protein cross-linking

近期论文

查看导师新发文章（温馨提示：请注意重名现象，建议点开原文通过作者单位确认）

Räz MH, Dexter HR, Millington CL, Van Loon B, Williams DM & Sturla SJ (2016) Bypass of mutagenic O6 -carboxymethylguanine DNA adducts by human Y- and B-family polymerases. Chem Res Toxicol, 29(9), 1493-1503. View this article in WRRO Wyss LA, Nilforoushan A, Williams DM, Marx A & Sturla SJ (2016) The use of an artificial nucleotide for polymerase-based recognition of carcinogenic O6 -alkylguanine DNA adducts. Nucleic Acids Res, 44(14), 6564-6573. View this article in WRRO Zhang F, Tsunoda M, Kikuchi Y, Wilkinson O, Millington CL, Margison GP, Williams DM & Takénaka A (2014) O⁶-carboxymethylguanine in DNA forms a sequence context-dependent wobble base-pair structure with thymine.. Acta Crystallogr D Biol Crystallogr, 70(Pt 6), 1669-1679. Zhang F, Tsunoda M, Suzuki K, Kikuchi Y, Wilkinson O, Millington CL, Margison GP, Williams DM, Czarina Morishita E & Takénaka A (2013) Structures of DNA duplexes containing O6-carboxymethylguanine, a lesion associated with gastrointestinal cancer, reveal a mechanism for inducing pyrimidine transition mutations.. Nucleic Acids Res, 41(10), 5524-5532. View this article in WRRO Wilkinson OJ, Latypov V, Tubbs JL, Millington CL, Morita R, Blackburn H, Marriott A, McGown G, Thorncroft M, Watson AJ, Connolly BA, Grasby JA, Masui R, Hunter CA, Tainer JA, Margison GP & Williams DM (2012) Alkyltransferase-like protein (Atl1) distinguishes alkylated guanines for DNA repair using cation-π interactions.. Proc Natl Acad Sci U S A, 109(46), 18755-18760. Abdu K, Aiertza MK, Wilkinson OJ, Grasby JA, Senthong P, Povey AC, Margison GP & Williams DM (2012) Synthesis of oligodeoxyribonucleotides containing a conformationally-locked anti analogue of O6-methyl-2'-deoxyguanosine and their recognition by MGMT and Atl1.. Chem Commun (Camb), 48(91), 11214-11216. Beddows A, Patel N, Finger LD, Atack JM, Williams DM & Grasby JA (2012) Interstrand disulfide crosslinking of DNA bases supports a double nucleotide unpairing mechanism for flap endonucleases.. Chem Commun (Camb), 48(71), 8895-8897.