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pilE G-Quadruplex Is Recognized and Preferentially Bound but Not Processed by the MutL Endonuclease from Neisseria gonorrhoeae Mismatch Repair Pathway

The human pathogen Neisseria gonorrhoeae uses a homologous recombination to undergo antigenic variation and avoid an immune response. The surface protein pilin (PilE) is one of the targets for antigenic variation that can be regulated by N. gonorrhoeae mismatch repair (MMR) and a G-quadruplex (G4) l...

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Autores principales: Savitskaya, Viktoriia Yu., Strekalovskikh, Vadim V., Snyga, Viktoriia G., Monakhova, Mayya V., Arutyunyan, Alexander M., Dolinnaya, Nina G., Kubareva, Elena A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10094033/
https://www.ncbi.nlm.nih.gov/pubmed/37047138
http://dx.doi.org/10.3390/ijms24076167
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author Savitskaya, Viktoriia Yu.
Strekalovskikh, Vadim V.
Snyga, Viktoriia G.
Monakhova, Mayya V.
Arutyunyan, Alexander M.
Dolinnaya, Nina G.
Kubareva, Elena A.
author_facet Savitskaya, Viktoriia Yu.
Strekalovskikh, Vadim V.
Snyga, Viktoriia G.
Monakhova, Mayya V.
Arutyunyan, Alexander M.
Dolinnaya, Nina G.
Kubareva, Elena A.
author_sort Savitskaya, Viktoriia Yu.
collection PubMed
description The human pathogen Neisseria gonorrhoeae uses a homologous recombination to undergo antigenic variation and avoid an immune response. The surface protein pilin (PilE) is one of the targets for antigenic variation that can be regulated by N. gonorrhoeae mismatch repair (MMR) and a G-quadruplex (G4) located upstream of the pilE promoter. Using bioinformatics tools, we found a correlation between pilE variability and deletion of DNA regions encoding ngMutS or ngMutL proteins, the main participants in N. gonorrhoeae methyl-independent MMR. To understand whether the G4 structure could affect the ngMutL-mediated regulation of pilin antigenic variation, we designed several synthetic pilE G4-containing oligonucleotides, differing in length, and related DNA duplexes. Using CD measurements and biochemical approaches, we have showed that (i) ngMutL preferentially binds to pilE G4 compared to DNA duplex, although the latter is a cognate substrate for ngMutL endonuclease, (ii) protein binding affinity decreases with shortening of quadruplex-containing and duplex ligands, (iii) the G4 structure inhibits ngMutL-induced DNA nicking and modulates cleavage positions; the enzyme does not cleave DNA within G4, but is able to bypass this noncanonical structure. Thus, pilE G4 may regulate the efficiency of pilin antigenic variation by quadruplex binding to ngMutL and suppression of homologous recombination.
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spelling pubmed-100940332023-04-13 pilE G-Quadruplex Is Recognized and Preferentially Bound but Not Processed by the MutL Endonuclease from Neisseria gonorrhoeae Mismatch Repair Pathway Savitskaya, Viktoriia Yu. Strekalovskikh, Vadim V. Snyga, Viktoriia G. Monakhova, Mayya V. Arutyunyan, Alexander M. Dolinnaya, Nina G. Kubareva, Elena A. Int J Mol Sci Article The human pathogen Neisseria gonorrhoeae uses a homologous recombination to undergo antigenic variation and avoid an immune response. The surface protein pilin (PilE) is one of the targets for antigenic variation that can be regulated by N. gonorrhoeae mismatch repair (MMR) and a G-quadruplex (G4) located upstream of the pilE promoter. Using bioinformatics tools, we found a correlation between pilE variability and deletion of DNA regions encoding ngMutS or ngMutL proteins, the main participants in N. gonorrhoeae methyl-independent MMR. To understand whether the G4 structure could affect the ngMutL-mediated regulation of pilin antigenic variation, we designed several synthetic pilE G4-containing oligonucleotides, differing in length, and related DNA duplexes. Using CD measurements and biochemical approaches, we have showed that (i) ngMutL preferentially binds to pilE G4 compared to DNA duplex, although the latter is a cognate substrate for ngMutL endonuclease, (ii) protein binding affinity decreases with shortening of quadruplex-containing and duplex ligands, (iii) the G4 structure inhibits ngMutL-induced DNA nicking and modulates cleavage positions; the enzyme does not cleave DNA within G4, but is able to bypass this noncanonical structure. Thus, pilE G4 may regulate the efficiency of pilin antigenic variation by quadruplex binding to ngMutL and suppression of homologous recombination. MDPI 2023-03-24 /pmc/articles/PMC10094033/ /pubmed/37047138 http://dx.doi.org/10.3390/ijms24076167 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Savitskaya, Viktoriia Yu.
Strekalovskikh, Vadim V.
Snyga, Viktoriia G.
Monakhova, Mayya V.
Arutyunyan, Alexander M.
Dolinnaya, Nina G.
Kubareva, Elena A.
pilE G-Quadruplex Is Recognized and Preferentially Bound but Not Processed by the MutL Endonuclease from Neisseria gonorrhoeae Mismatch Repair Pathway
title pilE G-Quadruplex Is Recognized and Preferentially Bound but Not Processed by the MutL Endonuclease from Neisseria gonorrhoeae Mismatch Repair Pathway
title_full pilE G-Quadruplex Is Recognized and Preferentially Bound but Not Processed by the MutL Endonuclease from Neisseria gonorrhoeae Mismatch Repair Pathway
title_fullStr pilE G-Quadruplex Is Recognized and Preferentially Bound but Not Processed by the MutL Endonuclease from Neisseria gonorrhoeae Mismatch Repair Pathway
title_full_unstemmed pilE G-Quadruplex Is Recognized and Preferentially Bound but Not Processed by the MutL Endonuclease from Neisseria gonorrhoeae Mismatch Repair Pathway
title_short pilE G-Quadruplex Is Recognized and Preferentially Bound but Not Processed by the MutL Endonuclease from Neisseria gonorrhoeae Mismatch Repair Pathway
title_sort pile g-quadruplex is recognized and preferentially bound but not processed by the mutl endonuclease from neisseria gonorrhoeae mismatch repair pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10094033/
https://www.ncbi.nlm.nih.gov/pubmed/37047138
http://dx.doi.org/10.3390/ijms24076167
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