Detail
Article
Online article
FT
Medvik - BMC
  • Something wrong with this record ?

Importance of base-pair opening for mismatch recognition

T. Bouchal, I. Durník, V. Illík, K. Réblová, P. Kulhánek,

. 2020 ; 48 (20) : 11322-11334. [pub] 20201118

Language English Country Great Britain

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc20027640

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.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc20027640
003      
CZ-PrNML
005      
20210114152149.0
007      
ta
008      
210105s2020 xxk f 000 0|eng||
009      
AR
024    7_
$a 10.1093/nar/gkaa896 $2 doi
035    __
$a (PubMed)33080020
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxk
100    1_
$a Bouchal, Tomáš $u CEITEC - Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic. National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic.
245    10
$a Importance of base-pair opening for mismatch recognition / $c T. Bouchal, I. Durník, V. Illík, K. Réblová, P. Kulhánek,
520    9_
$a 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.
650    12
$a chybné párování bází $7 D020137
650    _2
$a párování bází $7 D020029
650    _2
$a výpočetní biologie $7 D019295
650    _2
$a DNA $x chemie $x metabolismus $7 D004247
650    12
$a oprava chybného párování bází DNA $7 D053843
650    _2
$a vodíková vazba $7 D006860
650    12
$a simulace molekulární dynamiky $7 D056004
650    _2
$a vazebný protein MutS opravné syntézy DNA $x chemie $x genetika $x metabolismus $7 D051719
650    _2
$a termodynamika $7 D013816
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Durník, Ivo $u CEITEC - Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic. National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic.
700    1_
$a Illík, Viktor $u National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic.
700    1_
$a Réblová, Kamila $u CEITEC - Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic.
700    1_
$a Kulhánek, Petr $u CEITEC - Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic. National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic.
773    0_
$w MED00003554 $t Nucleic acids research $x 1362-4962 $g Roč. 48, č. 20 (2020), s. 11322-11334
856    41
$u https://pubmed.ncbi.nlm.nih.gov/33080020 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20210105 $b ABA008
991    __
$a 20210114152148 $b ABA008
999    __
$a ok $b bmc $g 1607975 $s 1118820
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2020 $b 48 $c 20 $d 11322-11334 $e 20201118 $i 1362-4962 $m Nucleic acids research $n Nucleic Acids Res $x MED00003554
LZP    __
$a Pubmed-20210105

Find record

Citation metrics

Logged in users only

Archiving options