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Elaine Davis group project:

DNA repair

One of the bacterial components that are damaged following activation of the macrophage is DNA. Whilst damaged lipids and proteins can be replaced, it is essential that damaged DNA is repaired to avoid mutation and to ensure that replication can proceed.

To investigate the role of DNA repair genes in M. tuberculosis pathogenesis, we have constructed a panel of strains in which individual DNA repair genes have been inactivated by allelic exchange. The phenotypes of these mutant strains are being compared with that of the wild-type following DNA damaging stresses in vitro and in models of infection. By targeting members of different DNA repair pathways, we hope to gain an insight into their relative importance.

The identification of DNA repair genes affecting virulence, coupled with the definition of their in vitro susceptibility to particular kinds of DNA damaging agents, will shed light on the conditions to which M. tuberculosis is exposed during infection.

Part of our research on the significance of DNA repair in M. tuberculosis has been funded by the EU FP6 programme within the consortium CSI-LTB (contract no 037235).

Collaborators

Prof. E. C. Böttger, Institut für Medizinische Mikrobiologie, Universität Zürich, Switzerland
Dr. B. Springer, Institut für Medizinische Mikrobiologie und Hygiene, Graz, Austria
Prof. M. Rizzi, DiSCAFF - University of Piemonte Orientale "A Avogadro", Novara, Italy
Prof. K. Muniyappa, Indian Institute of Science, Bangalore, India

Selected publications

Singh, P; Patil, KN; Khanduja, JS; Kumar, PS; Williams, A; Rossi, F; Rizzi, M; Davis, EO and Muniyappa, K (2010)
Mycobacterium tuberculosis UvrD1 and UvrA proteins suppress DNA strand exchange promoted by cognate and non-cognate RecA proteins.
Biochemistry 49, 4872-4883 PubMed abstract
Güthlein, C; Wanner, RM; Sander, P; Davis, EO; Bosshard, M; Jiricny, J; Böttger, EC and Springer, B (2009)
Characterisation of the mycobacterial NER system reveals novel functions of uvrD1 helicase.
Journal of Bacteriology 191, 555-562 PubMed abstract
Davis, EO and Forse, LN (2009)
DNA Repair: Key to Survival?
In: Mycobacterium: Genomics and Molecular Biology ,
Norwich, Caister Academic Press