Conserved motifs of MutL proteins

Banasik, Michał; Sachadyn, Paweł

doi:10.1016/j.mrfmmm.2014.07.006

Cited by 15 publications

(15 citation statements)

References 43 publications

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“…To date, the correction of mismatched nucleobases has been defined as a highly conserved mechanism whose key steps are performed, in all cases, by members of the MutS and MutL protein families. Despite the genomes of Crenarchaeota, a few groups of Euryarchaeota and almost all members of the phylum Actinobacteria lacking identifiable MutS or MutL homologues 5 6 7 , they exhibit rates and spectra of spontaneous mutations similar to canonical MMR-bearing bacterial species 8 9 10 , suggesting the existence of still undetected pathway responsible for this type of correction. Although recent biochemical and structural reports suggested the existence of a novel mismatch-specific endonuclease, NucS, in the archaeal species T. kodakarensis 12 14 that is able to recognize and cleave mismatched bases in dsDNA in vitro , no genetic and/or biological evidence had been reported to date on the activity of a novel mismatch repair pathway.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, despite the quasi -ubiquitous nature of this pathway, there are some important exceptions. The genomes of many Archaea, including Crenarchaeota and a few groups of Euryarchaeota, and almost all members of the bacterial phylum Actinobacteria, including Mycobacterium , have been shown to possess no identifiable MutS or MutL homologues 5 6 7 . However, these prokaryotes exhibit rates and spectra of spontaneous mutations similar to canonical MMR-bearing bacterial species 8 9 10 , suggesting the existence of unidentified mechanisms responsible for mismatch repair.…”

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confidence: 99%

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A non-canonical mismatch repair pathway in prokaryotes

et al. 2017

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Mismatch repair (MMR) is a near ubiquitous pathway, essential for the maintenance of genome stability. Members of the MutS and MutL protein families perform key steps in mismatch correction. Despite the major importance of this repair pathway, MutS–MutL are absent in almost all Actinobacteria and many Archaea. However, these organisms exhibit rates and spectra of spontaneous mutations similar to MMR-bearing species, suggesting the existence of an alternative to the canonical MutS–MutL-based MMR. Here we report that Mycobacterium smegmatis NucS/EndoMS, a putative endonuclease with no structural homology to known MMR factors, is required for mutation avoidance and anti-recombination, hallmarks of the canonical MMR. Furthermore, phenotypic analysis of naturally occurring polymorphic NucS in a M. smegmatis surrogate model, suggests the existence of M. tuberculosis mutator strains. The phylogenetic analysis of NucS indicates a complex evolutionary process leading to a disperse distribution pattern in prokaryotes. Together, these findings indicate that distinct pathways for MMR have evolved at least twice in nature.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

A non-canonical mismatch repair pathway in prokaryotes

et al. 2017

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“…Crystallographic analyses on the C-terminal domain (CTD) of eukaryotic and bacterial MutL endonuclease have shown that the domain is composed of regulatory and dimerization subdomains (11, 26 -28). The dimerization subdomain contains the metal-binding site essential for the endonuclease activity (29), in which two zinc ions are coordinated by the residues from highly conserved motifs: DQHAX 2 EX 4 E, ACR, and CPHGRP (11,15,26,30). These motifs are conserved in MutL from the majority of organisms except for limited species in ␥-proteobacteria (12, 15, 16, 19 -21, 31).…”

Section: Dna Mismatch Repair (Mmr)mentioning

confidence: 99%

Structural Features and Functional Dependency on β-Clamp Define Distinct Subfamilies of Bacterial Mismatch Repair Endonuclease MutL

Fukui

Baba

Kumasaka

et al. 2016

Journal of Biological Chemistry

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In early reactions of DNA mismatch repair, MutS recognizes mismatched bases and activates MutL endonuclease to incise the error-containing strand of the duplex. DNA sliding clamp is responsible for directing the MutL-dependent nicking to the newly synthesized/error-containing strand. In Bacillus subtilis MutL, the ␤-clamp-interacting motif (␤ motif) of the C-terminal domain (CTD) is essential for both in vitro direct interaction with ␤-clamp and in vivo repair activity. A large cluster of negatively charged residues on the B. subtilis MutL CTD prevents nonspecific DNA binding until ␤ clamp interaction neutralizes the negative charge. We found that there are some bacterial phyla whose MutL endonucleases lack the ␤ motif. For example, the region corresponding to the ␤ motif is completely missing in Aquifex aeolicus MutL, and critical amino acid residues in the ␤ motif are not conserved in Thermus thermophilus MutL. We then revealed the 1.35 Å-resolution crystal structure of A. aeolicus MutL CTD, which lacks the ␤ motif but retains the metalbinding site for the endonuclease activity. Importantly, there was no negatively charged cluster on its surface. It was confirmed that CTDs of ␤ motif-lacking MutLs, A. aeolicus MutL and T. thermophilus MutL, efficiently incise DNA even in the absence of ␤-clamp and that ␤-clamp shows no detectable enhancing effect on their activity. In contrast, CTD of Streptococcus mutans, a ␤ motif-containing MutL, required ␤-clamp for the digestion of DNA. We propose that MutL endonucleases are divided into three subfamilies on the basis of their structural features and dependence on ␤-clamp.

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“…Defects in the MMR system could therefore lead to highly elevated mutation rates (hypermutability), meiotic defects and infertility ( Harfe and Jinks-Robertson, 2000 ; Surtees et al, 2004 ). The genus Mycobacterium has no homologs of MutS or MutL ( Mizrahi and Andersen, 1998 ; Sachadyn, 2010 ; Banasik and Sachadyn, 2014 ). Instead, its genome stability is maintained via an alternative NucS pathway that appears in many Archaea ( Castaneda-Garcia et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Role of the DNA Mismatch Repair Gene MutS4 in Driving the Evolution of Mycobacterium yongonense Type I via Homologous Recombination

Kim

Kook

et al. 2017

Front. Microbiol.

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We recently showed that Mycobacterium yongonense could be divided into two genotypes: Type I, in which the rpoB gene has been transferred from Mycobacterium parascrofulaceum, and Type II, in which the rpoB gene has not been transferred. Comparative genome analysis of three M. yongonense Type I, two M. yongonense Type II and M. parascrofulaceum type strains were performed in this study to gain insight into gene transfer from M. parascrofulaceum into M. yongonense Type I strains. We found two genome regions transferred from M. parascrofulaceum: one contained 3 consecutive genes, including the rpoBC operon, and the other contained 57 consecutive genes that had been transferred into M. yongonense Type I genomes via homologous recombination. Further comparison between the M. yongonense Type I and II genomes revealed that Type I, but not Type II has a distinct DNA mismatch repair gene (MutS4 subfamily) that was possibly transferred via non-homologous recombination from other actinomycetes. We hypothesized that it could facilitate homologous recombination from the M. parascrofulaceum to the M. yongonense Type I genomes. We therefore generated recombinant Mycobacterium smegmatis containing a MutS4 operon of M. yongonense. We found that the M. tuberculosis rpoB fragment with a rifampin resistance-conferring mutation was more frequently inserted into recombinant M. smegmatis than the wild type, suggesting that MutS4 is a driving force in the gene transfer from M. parascrofulaceum to M. yongonense Type I strains via homologous recombination. In conclusion, our data indicated that MutS4 in M. yongonense Type I genomes may drive gene transfer from M. parascrofulaceum via homologous recombination, resulting in division of M. yongonense into two genotypes, Type I and II.

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Conserved motifs of MutL proteins

Cited by 15 publications

References 43 publications

A non-canonical mismatch repair pathway in prokaryotes

A non-canonical mismatch repair pathway in prokaryotes

Structural Features and Functional Dependency on β-Clamp Define Distinct Subfamilies of Bacterial Mismatch Repair Endonuclease MutL

Role of the DNA Mismatch Repair Gene MutS4 in Driving the Evolution of Mycobacterium yongonense Type I via Homologous Recombination

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