Importance of base-pair opening for mismatch recognition

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F20%3A00114694" target="_blank" >RIV/00216224:14310/20:00114694 - isvavai.cz</a>

Result on the web

<a href="https://doi.org/10.1093/nar/gkaa896" target="_blank" >https://doi.org/10.1093/nar/gkaa896</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/nar/gkaa896" target="_blank" >10.1093/nar/gkaa896</a>

Result language

angličtina

Original language name

Importance of base-pair opening for mismatch recognition

Original language description

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.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Nucleic Acids Research

ISSN

0305-1048

e-ISSN

1362-4962

Volume of the periodical

48

Issue of the periodical within the volume

20

Country of publishing house

GB - UNITED KINGDOM

Number of pages

13

Pages from-to

11322-11334

UT code for WoS article

000606018600014

EID of the result in the Scopus database

2-s2.0-85096355782