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Importance of base-pair opening for mismatch recognition
- Source :
- Nucleic Acids Research
- Publication Year :
- 2020
- Publisher :
- Oxford University Press, 2020.
-
Abstract
- Mismatch repair is a highly conserved cellular pathway responsible for repairing mismatched dsDNA. Errors are detected by the MutS enzyme, which most likely senses altered mechanical property of damaged dsDNA rather than a specific molecular pattern. While the curved shape of dsDNA in crystallographic MutS/DNA structures suggests the role of DNA bending, the theoretical support is not fully convincing. Here, we present a computational study focused on a base-pair opening into the minor groove, a specific base-pair motion observed upon interaction with MutS. Propensities for the opening were evaluated in terms of two base-pair parameters: Opening and Shear. We tested all possible base pairs in anti/anti, anti/syn and syn/anti orientations and found clear discrimination between mismatches and canonical base-pairs only for the opening into the minor groove. Besides, the discrimination gap was also confirmed in hotspot and coldspot sequences, indicating that the opening could play a more significant role in the mismatch recognition than previously recognized. Our findings can be helpful for a better understanding of sequence-dependent mutability. Further, detailed structural characterization of mismatches can serve for designing anti-cancer drugs targeting mismatched base pairs.
- Subjects :
- Base pair
AcademicSubjects/SCI00010
Base Pair Mismatch
Biology
Molecular Dynamics Simulation
01 natural sciences
DNA Mismatch Repair
03 medical and health sciences
chemistry.chemical_compound
0103 physical sciences
Genetics
Dna bending
Base Pairing
030304 developmental biology
0303 health sciences
Mechanical property
010304 chemical physics
Computational Biology
Hydrogen Bonding
DNA
MutS DNA Mismatch-Binding Protein
DNA metabolism
chemistry
Biophysics
Thermodynamics
DNA mismatch repair
Minor groove
Subjects
Details
- Language :
- English
- ISSN :
- 13624962 and 03051048
- Volume :
- 48
- Issue :
- 20
- Database :
- OpenAIRE
- Journal :
- Nucleic Acids Research
- Accession number :
- edsair.doi.dedup.....18f9ffdcf95e8568b7863b2785b393b4