Impact of the Nucleosome Histone Core on the Structure and Dynamics of DNA-Containing Pyrimidine-Pyrimidone (6-4) Photoproduct

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22310%2F20%3A43921724" target="_blank" >RIV/60461373:22310/20:43921724 - isvavai.cz</a>

Výsledek na webu

<a href="https://pubs.acs.org/doi/abs/10.1021/acs.jctc.0c00593" target="_blank" >https://pubs.acs.org/doi/abs/10.1021/acs.jctc.0c00593</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jctc.0c00593" target="_blank" >10.1021/acs.jctc.0c00593</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Impact of the Nucleosome Histone Core on the Structure and Dynamics of DNA-Containing Pyrimidine-Pyrimidone (6-4) Photoproduct

Popis výsledku v původním jazyce

The pyrimidine-pyrimidone (6-4) photoproduct (64-PP) is an important photoinduced DNA lesion constituting a mutational signature for melanoma. The structural impact of 64-PP on DNA complexed with histones affects the lesion mutagenicity and repair but remains poorly understood. Here we investigate the conformational dynamics of DNA-containing 64-PP within the nucleosome core particle by atomic-resolution molecular dynamics simulations and multiscale data analysis. We demonstrate that the histone core exerts important mechanical restraints that largely decrease global DNA structural fluctuations. However, the local DNA flexibility at the damaged site is enhanced due to imperfect structural adaptation to restraints imposed by the histone core. If 64-PP faces the histone core and is therefore not directly accessible by the repair protein, the complementary strand facing the solvent is deformed and exhibits higher flexibility than the corresponding strand in a naked, undamaged DNA. This may serve as an initial recognition signal for repair. Our simulations also pinpoint the structural role of proximal residues from the truncated histone tails. Copyright © 2020 American Chemical Society.

Název v anglickém jazyce

Impact of the Nucleosome Histone Core on the Structure and Dynamics of DNA-Containing Pyrimidine-Pyrimidone (6-4) Photoproduct

Popis výsledku anglicky

The pyrimidine-pyrimidone (6-4) photoproduct (64-PP) is an important photoinduced DNA lesion constituting a mutational signature for melanoma. The structural impact of 64-PP on DNA complexed with histones affects the lesion mutagenicity and repair but remains poorly understood. Here we investigate the conformational dynamics of DNA-containing 64-PP within the nucleosome core particle by atomic-resolution molecular dynamics simulations and multiscale data analysis. We demonstrate that the histone core exerts important mechanical restraints that largely decrease global DNA structural fluctuations. However, the local DNA flexibility at the damaged site is enhanced due to imperfect structural adaptation to restraints imposed by the histone core. If 64-PP faces the histone core and is therefore not directly accessible by the repair protein, the complementary strand facing the solvent is deformed and exhibits higher flexibility than the corresponding strand in a naked, undamaged DNA. This may serve as an initial recognition signal for repair. Our simulations also pinpoint the structural role of proximal residues from the truncated histone tails. Copyright © 2020 American Chemical Society.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10201 - Computer sciences, information science, bioinformathics (hardware development to be 2.2, social aspect to be 5.8)

Projekt

<a href="/cs/project/GA17-14683S" target="_blank" >GA17-14683S: Mechanické vlastnosti strukturních prvků RNA a DNA</a><br>

Návaznosti

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

Rok uplatnění

2020

Kód důvěrnosti údajů

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

Název periodika

Journal of Chemical Theory and Computation

ISSN

1549-9618

e-ISSN

—

Svazek periodika

16

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

5972-5981

Kód UT WoS článku

000570012000044

EID výsledku v databázi Scopus

2-s2.0-85090507456