Responses of DNA Mismatch Repair Proteins to a Stable G-Quadruplex Embedded into a DNA Duplex Structure
DNA mismatch repair (MMR) plays a crucial role in the maintenance of genomic stability. The main MMR protein, MutS, was recently shown to recognize the G-quadruplex (G4) DNA structures, which, along with regulatory functions, have a negative impact on genome integrity. Here, we studied the effect of...
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doaj-0fc4c203ba9641169340eb92738c50652020-11-25T04:09:43ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-11-01218773877310.3390/ijms21228773Responses of DNA Mismatch Repair Proteins to a Stable G-Quadruplex Embedded into a DNA Duplex StructureAnzhela V. Pavlova0Mayya V. Monakhova1Anna M. Ogloblina2Natalia A. Andreeva3Gennady Yu. Laptev4Vladimir I. Polshakov5Elizaveta S. Gromova6Maria I. Zvereva7Marianna G. Yakubovskaya8Tatiana S. Oretskaya9Elena A. Kubareva10Nina G. Dolinnaya11Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1, 119991 Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Leninskie Gory 1, 119991 Moscow, RussiaInstitute of Carcinogenesis, N.N. Blokhin NMRCO, Kashirskoe Shosse 24, 115478 Moscow, RussiaDepartment of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1, 119991 Moscow, RussiaDepartment of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1, 119991 Moscow, RussiaFaculty of Fundamental Medicine, Lomonosov Moscow State University, Lomonosovsky Avenue 27/1, 119991 Moscow, RussiaDepartment of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1, 119991 Moscow, RussiaDepartment of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1, 119991 Moscow, RussiaInstitute of Carcinogenesis, N.N. Blokhin NMRCO, Kashirskoe Shosse 24, 115478 Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Leninskie Gory 1, 119991 Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Leninskie Gory 1, 119991 Moscow, RussiaDepartment of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1, 119991 Moscow, RussiaDNA mismatch repair (MMR) plays a crucial role in the maintenance of genomic stability. The main MMR protein, MutS, was recently shown to recognize the G-quadruplex (G4) DNA structures, which, along with regulatory functions, have a negative impact on genome integrity. Here, we studied the effect of G4 on the DNA-binding activity of MutS from <i>Rhodobacter sphaeroides</i> (methyl-independent MMR) in comparison with MutS from <i>Escherichia coli</i> (methyl-directed MMR) and evaluated the influence of a G4 on the functioning of other proteins involved in the initial steps of MMR. For this purpose, a new DNA construct was designed containing a biologically relevant intramolecular stable G4 structure flanked by double-stranded regions with the set of DNA sites required for MMR initiation. The secondary structure of this model was examined using NMR spectroscopy, chemical probing, fluorescent indicators, circular dichroism, and UV spectroscopy. The results unambiguously showed that the d(GGGT)<sub>4</sub> motif, when embedded in a double-stranded context, adopts a G4 structure of a parallel topology. Despite strong binding affinities of MutS and MutL for a G4, the latter is not recognized by <i>E. coli</i> MMR as a signal for repair, but does not prevent MMR processing when a G4 and G/T mismatch are in close proximity.https://www.mdpi.com/1422-0067/21/22/8773G-quadruplexDNA mismatch repairMutSMutLMutHprotein–DNA binding |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Anzhela V. Pavlova Mayya V. Monakhova Anna M. Ogloblina Natalia A. Andreeva Gennady Yu. Laptev Vladimir I. Polshakov Elizaveta S. Gromova Maria I. Zvereva Marianna G. Yakubovskaya Tatiana S. Oretskaya Elena A. Kubareva Nina G. Dolinnaya |
spellingShingle |
Anzhela V. Pavlova Mayya V. Monakhova Anna M. Ogloblina Natalia A. Andreeva Gennady Yu. Laptev Vladimir I. Polshakov Elizaveta S. Gromova Maria I. Zvereva Marianna G. Yakubovskaya Tatiana S. Oretskaya Elena A. Kubareva Nina G. Dolinnaya Responses of DNA Mismatch Repair Proteins to a Stable G-Quadruplex Embedded into a DNA Duplex Structure International Journal of Molecular Sciences G-quadruplex DNA mismatch repair MutS MutL MutH protein–DNA binding |
author_facet |
Anzhela V. Pavlova Mayya V. Monakhova Anna M. Ogloblina Natalia A. Andreeva Gennady Yu. Laptev Vladimir I. Polshakov Elizaveta S. Gromova Maria I. Zvereva Marianna G. Yakubovskaya Tatiana S. Oretskaya Elena A. Kubareva Nina G. Dolinnaya |
author_sort |
Anzhela V. Pavlova |
title |
Responses of DNA Mismatch Repair Proteins to a Stable G-Quadruplex Embedded into a DNA Duplex Structure |
title_short |
Responses of DNA Mismatch Repair Proteins to a Stable G-Quadruplex Embedded into a DNA Duplex Structure |
title_full |
Responses of DNA Mismatch Repair Proteins to a Stable G-Quadruplex Embedded into a DNA Duplex Structure |
title_fullStr |
Responses of DNA Mismatch Repair Proteins to a Stable G-Quadruplex Embedded into a DNA Duplex Structure |
title_full_unstemmed |
Responses of DNA Mismatch Repair Proteins to a Stable G-Quadruplex Embedded into a DNA Duplex Structure |
title_sort |
responses of dna mismatch repair proteins to a stable g-quadruplex embedded into a dna duplex structure |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2020-11-01 |
description |
DNA mismatch repair (MMR) plays a crucial role in the maintenance of genomic stability. The main MMR protein, MutS, was recently shown to recognize the G-quadruplex (G4) DNA structures, which, along with regulatory functions, have a negative impact on genome integrity. Here, we studied the effect of G4 on the DNA-binding activity of MutS from <i>Rhodobacter sphaeroides</i> (methyl-independent MMR) in comparison with MutS from <i>Escherichia coli</i> (methyl-directed MMR) and evaluated the influence of a G4 on the functioning of other proteins involved in the initial steps of MMR. For this purpose, a new DNA construct was designed containing a biologically relevant intramolecular stable G4 structure flanked by double-stranded regions with the set of DNA sites required for MMR initiation. The secondary structure of this model was examined using NMR spectroscopy, chemical probing, fluorescent indicators, circular dichroism, and UV spectroscopy. The results unambiguously showed that the d(GGGT)<sub>4</sub> motif, when embedded in a double-stranded context, adopts a G4 structure of a parallel topology. Despite strong binding affinities of MutS and MutL for a G4, the latter is not recognized by <i>E. coli</i> MMR as a signal for repair, but does not prevent MMR processing when a G4 and G/T mismatch are in close proximity. |
topic |
G-quadruplex DNA mismatch repair MutS MutL MutH protein–DNA binding |
url |
https://www.mdpi.com/1422-0067/21/22/8773 |
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