Photoinduced charge separation and DNA self-repair depend on sequence directionality and stacking pattern

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F24%3A00600749" target="_blank" >RIV/68081707:_____/24:00600749 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15640/24:73624534

Výsledek na webu

<a href="https://pubs.rsc.org/en/content/articlelanding/2024/sc/d3sc04971j" target="_blank" >https://pubs.rsc.org/en/content/articlelanding/2024/sc/d3sc04971j</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/d3sc04971j" target="_blank" >10.1039/d3sc04971j</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Photoinduced charge separation and DNA self-repair depend on sequence directionality and stacking pattern

Popis výsledku v původním jazyce

Charge separation is one of the most common consequences of the absorption of UV light by DNA. Recently, it has been shown that this process can enable efficient self-repair of cyclobutane pyrimidine dimers (CPDs) in specific short DNA oligomers such as the GAT00000000000000000000000000000000111111110000000011111111000000000000000000000000T sequence. The mechanism was characterized as sequential electron transfer through the nucleobase stack which is controlled by the redox potentials of nucleobases and their sequence. Here, we demonstrate that the inverse sequence TTAG promotes self-repair with higher quantum yields (0.58 +/- 0.23%) than GATT (0.44 +/- 0.18%) in a comparative study involving UV-irradiation experiments. After extended exposure to UV irradiation, a photostationary equilibrium between self-repair and damage formation is reached at 33 +/- 13% for GATT and at 40 +/- 16% for TTAG, which corresponds to the maximum total yield of self-repair. Molecular dynamics and quantum mechanics/molecular mechanics (QM/MM) simulations allowed us to assign this disparity to better stacking overlap between the G and A bases, which lowers the energies of the key A-G+ charge transfer state in the dominant conformers of the TTAG tetramer. These conformational differences also hinder alternative photorelaxation pathways of the TTAG tetranucleotide, which otherwise compete with the sequential electron transfer mechanism responsible for CPD self-repair. Overall, we demonstrate that photoinduced electron transfer is strongly dependent on conformation and the availability of alternative photodeactivation mechanisms. This knowledge can be used in the identification and prediction of canonical and modified DNA sequences exhibiting efficient electron transfer. It also further contributes to our understanding of DNA self-repair and its potential role in the photochemical selection of the most photostable sequences on the early Earth.

Název v anglickém jazyce

Photoinduced charge separation and DNA self-repair depend on sequence directionality and stacking pattern

Popis výsledku anglicky

Charge separation is one of the most common consequences of the absorption of UV light by DNA. Recently, it has been shown that this process can enable efficient self-repair of cyclobutane pyrimidine dimers (CPDs) in specific short DNA oligomers such as the GAT00000000000000000000000000000000111111110000000011111111000000000000000000000000T sequence. The mechanism was characterized as sequential electron transfer through the nucleobase stack which is controlled by the redox potentials of nucleobases and their sequence. Here, we demonstrate that the inverse sequence TTAG promotes self-repair with higher quantum yields (0.58 +/- 0.23%) than GATT (0.44 +/- 0.18%) in a comparative study involving UV-irradiation experiments. After extended exposure to UV irradiation, a photostationary equilibrium between self-repair and damage formation is reached at 33 +/- 13% for GATT and at 40 +/- 16% for TTAG, which corresponds to the maximum total yield of self-repair. Molecular dynamics and quantum mechanics/molecular mechanics (QM/MM) simulations allowed us to assign this disparity to better stacking overlap between the G and A bases, which lowers the energies of the key A-G+ charge transfer state in the dominant conformers of the TTAG tetramer. These conformational differences also hinder alternative photorelaxation pathways of the TTAG tetranucleotide, which otherwise compete with the sequential electron transfer mechanism responsible for CPD self-repair. Overall, we demonstrate that photoinduced electron transfer is strongly dependent on conformation and the availability of alternative photodeactivation mechanisms. This knowledge can be used in the identification and prediction of canonical and modified DNA sequences exhibiting efficient electron transfer. It also further contributes to our understanding of DNA self-repair and its potential role in the photochemical selection of the most photostable sequences on the early Earth.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

Projekt

<a href="/cs/project/GA21-23718S" target="_blank" >GA21-23718S: Studium fascinující fyzikální chemie DNA pomocí pokročilých výpočetních metod</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

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

Název periodika

Chemical Science

ISSN

2041-6520

e-ISSN

2041-6539

Svazek periodika

15

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

9

Strana od-do

2158-2166

Kód UT WoS článku

001138279200001

EID výsledku v databázi Scopus

2-s2.0-85182366023