Insights into the Structure of Intrastrand Cross-Link DNA Lesion-Containing Oligonucleotides: G[8-5m]T and G[8-5]C from Molecular Dynamics Simulations

Kód výsledku v IS VaVaI

RIV/61388963:_____/15:00443583 - isvavai.cz

Výsledek na webu

http://dx.doi.org/10.1021/bi501157v

DOI - Digital Object Identifier

10.1021/bi501157v

Jazyk výsledku

angličtina

Název v původním jazyce

Insights into the Structure of Intrastrand Cross-Link DNA Lesion-Containing Oligonucleotides: G[8-5m]T and G[8-5]C from Molecular Dynamics Simulations

Popis výsledku v původním jazyce

Oxidatively generated complex DNA lesions occur more rarely than single-nucleotide defects, yet they play an important role in carcinogenesis and aging diseases because they have proved to be more mutagenic than simple lesions. Whereas their formation pathways are rather well understood, the field suffers from the absence of structural data that are crucial for interpreting the lack of repair. No experimental structures are available for oligonucleotides featuring such a lesion. Hence, the detailed structural basis of such damaged duplexes has remained elusive. We propose the use of explicit solvent molecular dynamics simulations to build up damaged oligonucleotides containing two intrastrand cross-link defects, namely, the guanine-thymine and guanine-cytosine defects. Each of these lesions, G[8-5m]T and G[8-5]C, is placed in the middle of a dodecameric sequence, which undergoes an important structural rearrangement that we monitor and analyze. In both duplexes, the structural evolutio

Název v anglickém jazyce

Insights into the Structure of Intrastrand Cross-Link DNA Lesion-Containing Oligonucleotides: G[8-5m]T and G[8-5]C from Molecular Dynamics Simulations

Popis výsledku anglicky

Oxidatively generated complex DNA lesions occur more rarely than single-nucleotide defects, yet they play an important role in carcinogenesis and aging diseases because they have proved to be more mutagenic than simple lesions. Whereas their formation pathways are rather well understood, the field suffers from the absence of structural data that are crucial for interpreting the lack of repair. No experimental structures are available for oligonucleotides featuring such a lesion. Hence, the detailed structural basis of such damaged duplexes has remained elusive. We propose the use of explicit solvent molecular dynamics simulations to build up damaged oligonucleotides containing two intrastrand cross-link defects, namely, the guanine-thymine and guanine-cytosine defects. Each of these lesions, G[8-5m]T and G[8-5]C, is placed in the middle of a dodecameric sequence, which undergoes an important structural rearrangement that we monitor and analyze. In both duplexes, the structural evolutio

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CF - Fyzikální chemie a teoretická chemie

OECD FORD obor

—

Projekt

GA14-21893S: Nanomechanika strukturních motivů RNA a DNA

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2015

Kód důvěrnosti údajů

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

Název periodika

Biochemistry

ISSN

0006-2960

e-ISSN

—

Svazek periodika

54

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

1259-1267

Kód UT WoS článku

000349574900012

EID výsledku v databázi Scopus

2-s2.0-84922616662