Mycobacteria exploit three genetically distinct DNA double-strand break repair pathways Journal Article
| Authors: | Gupta, R.; Barkan, D.; Redelman-Sidi, G.; Shuman, S.; Glickman, M. S. |
| Article Title: | Mycobacteria exploit three genetically distinct DNA double-strand break repair pathways |
| Abstract: | Bacterial pathogens rely on their DNA repair pathways to resist genomic damage inflicted by the host. DNA double-strand breaks (DSBs) are especially threatening to bacterial viability. DSB repair by homologous recombination (HR) requires nucleases that resect DSB ends and a strand exchange protein that facilitates homology search. RecBCD and RecA perform these functions in Escherichia coli and constitute the major pathway of error-free DSB repair. Mycobacteria, including the human pathogen M. tuberculosis, elaborate an additional error-prone pathway of DSB repair via non-homologous end-joining (NHEJ) catalysed by Ku and DNA ligase D (LigD). Little is known about the relative contributions of HR and NHEJ to mycobacterial chromosome repair, the factors that dictate pathway choice, or the existence of additional DSB repair pathways. Here we demonstrate that Mycobacterium smegmatis has three DSB repair pathway options: HR, NHEJ and a novel mechanism of single-strand annealing (SSA). Inactivation of NHEJ or SSA is compensated by elevated HR. We find that mycobacterial RecBCD does not participate in HR or confer resistance to ionizing radiation (IR), but is required for the RecA-independent SSA pathway. In contrast, the mycobacterial helicase-nuclease AdnAB participates in the RecA-dependent HR pathway, and is a major determinant of resistance to IR and oxidative DNA damage. These findings reveal distinctive features of mycobacterial DSB repair, most notably the dedication of the RecBCD and AdnAB helicase-nuclease machines to distinct repair pathways. © 2010 Blackwell Publishing Ltd. |
| Keywords: | signal transduction; controlled study; unclassified drug; nonhuman; protein function; dna damage; homologous recombination; dna repair; enzyme activity; genetic recombination; ionizing radiation; nuclease; double stranded dna break; oxidative stress; helicase; bacterial dna; mycobacterium smegmatis; protein adnab; exodeoxyribonuclease v; reca protein; bacterial metabolism; bacterial viability; non homologous end joining; nucleic acid renaturation; single strand annealing |
| Journal Title: | Molecular Microbiology |
| Volume: | 79 |
| Issue: | 2 |
| ISSN: | 0950-382X |
| Publisher: | Blackwell Publishing |
| Date Published: | 2011-01-01 |
| Start Page: | 316 |
| End Page: | 330 |
| Language: | English |
| DOI: | 10.1111/j.1365-2958.2010.07463.x |
| PROVIDER: | scopus |
| PUBMED: | 21219454 |
| PMCID: | PMC3812669 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 4 March 2011" - "CODEN: MOMIE" - "Source: Scopus" |
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