FINNEGAN, David - University of Edinburgh - School of Biological Sciences

个人简介

1977 - Present University of Edinburgh 1974 - 1977 Postdoctoral Fellow, Department of Biochemistry, Stanford University 1972 -1973 Postdoctoral Fellow, Genetics Laboratory, University of Oxford 1972 PhD, Department of Molecular Biology, University of Edinburgh

研究领域

Transposable elements are DNA sequences that move from one place to another within a genome. The availability of complete genome sequences has revealed the significant role that these elements play in genome evolution, organization and stability. They make up a substantial proportion of most genomes, over 40% in the case of the human genome. We have studied several aspects of the molecular biology of transposable elements and are particularly interested in how they transpose and how transposition is regulated. To this end we are using two transposable elements from Drosophila, the I factor, an element related to the LINE 1 elements that make up nearly 20% of the human genome, and mariner, an element related to those being developed as vectors for transgenesis and gene therapy. The I factor is a non-LTR retrotransposon that transposes in the female germ-line where its RNA transposition intermediate is transported along microtubules to the oocyte nucleus. Our current research, done in collaboration with Prof Ilan Davis in the University of Oxford, is directed towards understanding the cellular processes required for this transport, how transport of I factor RNA is related to transport of other RNAs within the cell, the steps in transposition that occur once this RNA has reached the nucleus, and the role that I factor encoded proteins play in transposition. The stem loop (top) shows the predicted secondary structure of the motif that allows I factor RNA to move to the oocyte nucleus. The micrograph (bottom) shows a Drosophila oocyte injected with fluorescently labelled RNA (red) containing this motif. RNA was injected in the centre of the oocyte and has moved to the anterior (left) and to the dorso-anterior corner (top left) where it forms a cap over the nucleus. The mariner transposon moves by a cut and paste mechanism during which a mariner encoded protein, transposase, excises it from one position in the genome and inserts it at another. Mariner transposase is a member of a family of enzymes that includes transposases of transposons found in bacteria, plants and fungi, retroviral integrases and the RAG recombinase that mediates immunoglobulin gene rearrangement. We are studying the steps, in transposase action biochemically, and in conjunction with Dr Julia Richardson and Prof Malcolm Walkinshaw in Edinburgh we are investigating this mechanism at the structural level.

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Hartswood E, Brodie J, Vendra G, Davis I, Finnegan DJ (2012) RNA:RNA Interaction Can Enhance RNA Localisation in Drosophila Oocytes. RNA 18: 729-737 Richardson JM, Colloms SD, Finnegan DJ, Walkinshaw MD (2009) Molecular architecture of the Mos1 paired-end complex: the structural basis of DNA transposition in a eukaryote. Cell 138: 1096-1108 Hamilton RS, Hartswood E, Vendra G, Jones C, Van De Bor V, Finnegan D, Davis I (2009) A bioinformatics search pipeline, RNA2DSearch, identifies RNA localization elements in Drosophila retrotransposons. RNA 15: 200-207 Schostak N, Pyatkov K, Zelentsova E, Arkhipova I, Shagin D, Shagina I, Mudrik E, Blintsov A, Clark I, Finnegan DJ, Evgen'ev M (2008) Molecular dissection of Penelope transposable element regulatory machinery. Nucleic Acids Res 36: 2522-2529 Clark, I.B., Jarman, A.P. and Finnegan, D.J. (2007) Live imaging of Drosophila gonad formation reveals roles for Six4 in regulating germline and somatic cell migration. BMC Dev Biol, 7, 52. Clark, I.B., Boyd, J., Hamilton, G., Finnegan, D.J. and Jarman, A.P. (2006) D-six4 plays a key role in patterning cell identities deriving from the Drosophila mesoderm. Dev Biol, 294, 220-231. Richardson, J.M., Dawson, A., O'Hagan, N., Taylor, P., Finnegan, D.J. and Walkinshaw, M.D. (2006) Mechanism of Mos1 transposition: insights from structural analysis. Embo J, 25, 1324-1334. Van De Bor, V., Hartswood, E., Jones, C., Finnegan, D. and Davis, I. (2005) gurken and the I Factor Retrotransposon RNAs Share Common Localization Signals and Machinery. Dev Cell, 9, 51-62. Pyatkov KI, Arkhipova IR, Malkova NV, Finnegan DJ, Evgen'ev MB (2004) Reverse transcriptase and endonuclease activities encoded by Penelope-like retroelements. Proc Natl Acad Sci U S A 101: 14719-14724 Dawson, A. and Finnegan, D.J. (2003) Excision of the Drosophila mariner transposon Mos1. Comparison with bacterial transposition and V(D)J recombination. Mol Cell, 11, 225-235.