The majority of inducible DNA repair genes in Mycobacterium tuberculosis are induced independently of RecA

Abstract

SummaryIn many species of bacteria most inducible DNA repair genes are regulated by LexA homologues and are dependent on RecA for induction. We have shown previously by analysing the induction of recA that two mechanisms for the induction of gene expression following DNA damage exist in Mycobacterium tuberculosis . Whereas one of these depends on RecA and LexA in the classical way, the other mechanism is independent of both of these proteins and induction occurs in the absence of RecA. Here we investigate the generality of each of these mechanisms by analysing the global response to DNA damage in both wild-type M. tuberculosis and a recA deletion strain of M. tuberculosis using microarrays. This revealed that the majority of the genes that were induced remained inducible in the recA mutant stain. Of particular note most of the inducible genes with known or predicted functions in DNA repair did not depend on recA for induction. Amongst these are genes involved in nucleotide excision repair, base excision repair, damage reversal and recombination. Thus, it appears that this novel mechanism of gene regulation is important for DNA repair in M. tuberculosis .

Important role of the nucleotide excision repair pathway in Mycobacterium smegmatis in conferring protection against commonly encountered DNA-damaging agents

“…It is significant that uvrA and uvrB are induced in mycobacteria upon treatment with DNA-damaging agents like mitomycin C as well as upon infecting human macrophages (Rand et al, 2003;Graham & Clark-Curtiss, 1999). Thus, NER seems to be central to DNA repair mechanisms in mycobacteria.…”

“…The genome sequences of M. tuberculosis (Cole et al, 1998), Mycobacterium leprae (Cole et al, 2001;Smith et al, 1997) and Mycobacterium smegmatis (http://www.tigr.org) have suggested that mismatch repair enzymes are missing in these organisms (Mizrahi & Andersen, 1998), and the role of RecA has been found to be minimal in mutation prevention (Boshoff et al, 2003;Rand et al, 2003). Thus, among the major DNA repair pathways, the base excision repair (BER) and the nucleotide excision repair (NER) pathways presumably contribute significantly to the maintenance of the genomic integrity in these bacteria.…”

Synergistic effects of UdgB and Ung in mutation prevention and protection against commonly encountered DNA damaging agents in Mycobacterium smegmatis

“…The genome sequences of Mycobacterium tuberculosis and Mycobacterium smegmatis have revealed that they lack the mismatch repair and the very short patch repair pathway enzymes (Cole et al, 1998;Mizrahi & Andersen, 1998). Furthermore, RecA-mediated repair also does not appear to play a significant role in mutation prevention in mycobacteria (Boshoff et al, 2003;Rand et al, 2003). Thus, the base-and nucleotide-excision repair pathways must play significant roles in maintaining genomic integrity in these bacteria (Kurthkoti et al, 2008).…”

A transcriptional response to replication status mediated by the conserved bacterial replication protein DnaA

“…RecA elicits the SOS response upon binding single-stranded DNA and stimulating the autocleavage of LexA (3). RecA-inducible, LexArepressible genes have been extensively characterized in several bacterial species including B. subtilis (5)(6)(7)(8). In B. subtilis, cell division and development (sporulation) are regulated, in part, by a RecAdependent mechanism (4,9).…”