Suppression of Homologous and Homeologous Recombination by the Bacterial MutS2 Protein

Abstract

In addition to their role in DNA repair, recombination events are associated with processes aimed at providing the genetic variability needed for adaptation and evolution of a population. In bacteria, recombination is involved in the appearance of new variants by allowing the incorporation of exogenous DNA or the reshuffling of endogenous sequences. Here we show that HpMutS2, a protein belonging to the MutS2 family in Helicobacter pylori, is not involved in mismatch repair but inhibits homologous and homeologous recombination. Disruption of HpmutS2 leads to an increased efficiency of exogenous DNA incorporation. HpMutS2 has a selective affinity for DNA structures mimicking recombination intermediates with no specificity for homoduplex DNA or mismatches. The purified protein has an ATPase activity stimulated by the same DNA structures. Finally, we show that HpMutS2 inhibits DNA strand exchange reactions in vitro. Thus, MutS2 proteins are candidates for controlling recombination and therefore genetic diversity in bacteria.

Crystal Structure of MutS2 Endonuclease Domain and the Mechanism of Homologous Recombination Suppression

“…3A). This result indicates that ttMutS2 is involved in the suppression of homologous recombination like H. pylori MutS2 (8,9). We examined the effect of ttmutS2 disruption on the resistance to mitomycin-C (MMC), which induces both DNA intrastrand and, to a greater extent, interstrand cross-links.…”

“…Recent studies have shown that bacterial and plant MutS2 proteins are candidate anti-recombination enzymes (8,9). MutS2 is a paralogue of Escherichia coli MutS, which recognizes a mismatched base pair and induces the mismatch repair (MMR) 2 pathway ( Fig.…”

“…It had been reported that eukaryotic MSH4 and MSH5 promote homologous recombination (13)(14)(15). In contrast, the disruption of Helicobacter pylori mutS2 increases the frequency of homologous recombination, indicating that H. pylori MutS2 suppresses homologous recombination (8,9). Moreover, it has been shown that purified H. pylori MutS2 binds to a DNA structure mimicking the Holliday junction and interferes with the strand-exchange reaction mediated by RecA in vitro (8).…”

“…In contrast, the disruption of Helicobacter pylori mutS2 increases the frequency of homologous recombination, indicating that H. pylori MutS2 suppresses homologous recombination (8,9). Moreover, it has been shown that purified H. pylori MutS2 binds to a DNA structure mimicking the Holliday junction and interferes with the strand-exchange reaction mediated by RecA in vitro (8). However, the mechanism by which MutS2 inhibits the strand-exchange reaction has been unknown.…”

Two new subfamilies of DNA mismatch repair proteins (MutS) specifically abundant in the marine environment

“…In this study, we use the following naming of the MutS subfamilies, which is adapted from the recent study by Lin et al (Lin et al, 2007). In total, 12 subfamilies were previously described to compose the MutS family: 'MutS1/ MSH1' including E. coli MutS and the mitochondria-targeted fungal MutS homolog 1 (MSH1); 'MutS2', known to inhibit recombination in H. pylori (Pinto et al, 2005) and to possess a C-terminal endonuclease domain called the small MutS-related (Smr) domain (Moreira and Philippe, 1999;Fukui et al, 2008); 'MSH2', 'MSH3', 'MSH4', 'MSH5' and 'MSH6/7', found in most eukaryotes (with the exception of MSH7 being a plant-specific paralogous group of MSH6 (Wu et al, 2003)); another plantspecific MSH1 (called 'plt-MSH1' hereafter) with the GIY-YIG endonuclease domain at their C-terminus (Abdelnoor et al, 2006); 'MutS3', 'MutS4' and 'MutS5', recently described but functionally uncharacterized prokaryotic homologs (Lin et al, 2007), and the above mentioned 'MutS7' subfamily represented by the Mimivirus MutS homolog.…”