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Chapter 31 : Double-Strand DNA Break Repair in Mycobacteria

Author: Michael S. Glickman1
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Affiliations: 1: Immunology Program, Sloan Kettering Institute and Infectious Diseases, Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065
Content Type: Monograph
Publication Year: 2014

Category: Microbial Genetics and Molecular Biology

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Abstract:

Repair of double-strand DNA breaks (DSBs) is critical to all living organisms. Scission of the phosphodiester backbone of both DNA strands is lethal if not repaired because such loss of linear chromosome integrity compromises chromosome replication and thereby prevents genome duplication. In contrast to some other types of DNA lesions which can be bypassed by damage-tolerant DNA polymerases, there is no known mechanism for the replication or transcription machinery to bypass a DSB, mandating their repair before replication or transcription can proceed. As such, multiple systems have evolved to repair DSBs, from bacterial to human cells ( ). In the past decade, mycobacterial DNA repair systems in general, and mycobacterial DSB repair systems in particular, have received increasing attention. It has become clear that mycobacterial DSB repair differs substantially from the standard models of prokaryotic DSB repair derived from work in the system. Most prominent among these differences is the existence of two additional DSB repair pathways that are not present in and were previously thought not to exist in bacteria: nonhomologous end joining (NHEJ) and single-strand annealing (SSA). Multiple other novel features of mycobacterial DSB repair have also been elucidated, making mycobacteria a new model system for the study of prokaryotic DSB repair. As now conceptualized, mycobacterial DSB repair actually most resembles DSB repair in budding yeast rather than other prokaryotes ( Table 1 ). In addition to its emerging place as a model system, studies of mycobacterial DNA repair also are of great importance for understanding mechanisms of mutagenesis and genome diversification in , the ultimate cause of antimicrobial resistance in ( ). In addition to the information and references contained in this article, the reader is pointed to several excellent recently published reviews of mycobacterial DNA repair and mutagenesis ( ).

Citation: Glickman M. 2014. Double-Strand DNA Break Repair in Mycobacteria, p 657-666. In Hatfull G, Jacobs W (ed), Molecular Genetics of Mycobacteria, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MGM2-0024-2013

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Double-Strand DNA Break Repair in Mycobacteria
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Citation: Glickman M. 2014. Double-Strand DNA Break Repair in Mycobacteria, p 657-666. In Hatfull G, Jacobs W (ed), Molecular Genetics of Mycobacteria, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MGM2-0024-2013
/content/10.1128/9781555818845.chap31.fig31-1
Figure 1

Pathways of DSB repair in mycobacteria. Our present understanding of DSB repair in mycobacteria. The three pathways shown are HR, NHEJ, and SSA. For each pathway, the major DNA processing events are depicted with the factors required for each step, when known. A question mark indicates that no specific experimental genetic data is available about that step, despite the presence of predicted proteins in mycobacterial chromosomes that may mediate these steps, or even biochemical activities consistent with a role in these pathways. In the NHEJ column the three outcomes below the arrow indicate faithful repair, nucleotide addition, and nucleotide trimming, respectively. In the SSA column, the blue rectangles indicate repeat sequences that flank the DSB. Please see text for further details and references. doi:10.1128/microbiolspec.MGM2-0024-2013.f1

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Image of Figure 1
Figure 1

Pathways of DSB repair in mycobacteria. Our present understanding of DSB repair in mycobacteria. The three pathways shown are HR, NHEJ, and SSA. For each pathway, the major DNA processing events are depicted with the factors required for each step, when known. A question mark indicates that no specific experimental genetic data is available about that step, despite the presence of predicted proteins in mycobacterial chromosomes that may mediate these steps, or even biochemical activities consistent with a role in these pathways. In the NHEJ column the three outcomes below the arrow indicate faithful repair, nucleotide addition, and nucleotide trimming, respectively. In the SSA column, the blue rectangles indicate repeat sequences that flank the DSB. Please see text for further details and references. doi:10.1128/microbiolspec.MGM2-0024-2013.f1

Citation: Glickman M. 2014. Double-Strand DNA Break Repair in Mycobacteria, p 657-666. In Hatfull G, Jacobs W (ed), Molecular Genetics of Mycobacteria, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MGM2-0024-2013
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Tables

Double-Strand DNA Break Repair in Mycobacteria
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Citation: Glickman M. 2014. Double-Strand DNA Break Repair in Mycobacteria, p 657-666. In Hatfull G, Jacobs W (ed), Molecular Genetics of Mycobacteria, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MGM2-0024-2013
/content/10.1128/9781555818845.chap31.tab31-1
Table 1

Comparison of DSB repair systems in bacteria and yeast

Generic image for table
Table 1

Comparison of DSB repair systems in bacteria and yeast

Citation: Glickman M. 2014. Double-Strand DNA Break Repair in Mycobacteria, p 657-666. In Hatfull G, Jacobs W (ed), Molecular Genetics of Mycobacteria, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MGM2-0024-2013

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