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J. Bacteriol. doi:10.1128/JB.00216-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Characterisation of the mycobacterial NER system reveals novel functions of uvrD1 helicase

Institut für Medizinische Mikrobiologie, University of Zurich, Gloriastr. 30/32, CH-8006 Zurich, Switzerland; Nationales Zentrum für Mykobakterien, Gloriastr. 30, CH-8006 Zurich, Switzerland; Division of Mycobacterial Research, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK; Institute of Molecular Cancer Research, University of Zurich, Winterthurerstr. 190, CH-8057 and Department of Biology, Swiss Federal Institutes of Technology (ETH), Zurich, Switzerland

^* To whom correspondence should be addressed. Email: boettger{at}immv.uzh.ch.

	Abstract

In this study, we investigated the role of the nucleotide excision repair (NER) pathway in mycobacterial DNA repair. Mycobacterium smegmatis lacking the NER excinuclease component uvrB, the helicase uvrD1 and a double knock-out lacking both proteins were constructed and their sensitivity to a series of DNA damaging agents was analysed. As anticipated, the mycobacterial NER system was shown to be involved in the processing of bulky DNA adducts and inter-strand cross-links. In addition, it could be shown to exert a protective effect against oxidising and nitrosating agents. Interestingly, inactivation of uvrB and uvrD1 significantly increased marker integration frequencies in gene conversion assays. This implies that in mycobacteria, which lack the postreplicative mismatch repair system, NER, and particularly the UvrD1 helicase, is involved in the processing of a subset of recombination-associated mismatches.