Sequential electron transfer governs the UV-induced self-repair of DNA photolesions

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F18%3A00492425" target="_blank" >RIV/68081707:_____/18:00492425 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15310/18:73591647

Výsledek na webu

<a href="http://dx.doi.org/10.1039/c8sc00024g" target="_blank" >http://dx.doi.org/10.1039/c8sc00024g</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/c8sc00024g" target="_blank" >10.1039/c8sc00024g</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Sequential electron transfer governs the UV-induced self-repair of DNA photolesions

Popis výsledku v původním jazyce

Cyclobutane pyrimidine dimers (CpDs) are among the most common DNA lesions occurring due to the interaction with ultraviolet light. While photolyases have been well known as external factors repairing CpDs, the intrinsic self-repairing capabilities of the GAT=T DNA sequence were discovered only recently and are still largely obscure. Here, we elucidate the mechanistic details of this self-repair process by means of MD simulations and QM/MM computations involving the algebraic diagrammatic construction to the second order [ADC(2)] method. We show that local UV-excitation of guanine may be followed by up to three subsequent electron transfers, which may eventually enable efficient CpD ring opening when the negative charge resides on the T=T dimer. Consequently, the molecular mechanism of GAT=T self-repair can be envisaged as sequential electron transfer (SET) occurring downhill along the slope of the S-1 potential energy surface. Even though the general features of the SET mechanism are retained in both of the studied stacked conformers, our optimizations of different S-1/S-0 state crossings revealed minor differences which could influence their self-repair efficiencies. We expect that such assessment of the availability and efficiency of the SET process in other DNA oligomers could hint towards other sequences exhibiting similar photochemical properties. Such explorations will be particularly fascinating in the context of the origins of biomolecules on Earth, owing to the lack of external repairing factors in the Archean age.

Název v anglickém jazyce

Sequential electron transfer governs the UV-induced self-repair of DNA photolesions

Popis výsledku anglicky

Cyclobutane pyrimidine dimers (CpDs) are among the most common DNA lesions occurring due to the interaction with ultraviolet light. While photolyases have been well known as external factors repairing CpDs, the intrinsic self-repairing capabilities of the GAT=T DNA sequence were discovered only recently and are still largely obscure. Here, we elucidate the mechanistic details of this self-repair process by means of MD simulations and QM/MM computations involving the algebraic diagrammatic construction to the second order [ADC(2)] method. We show that local UV-excitation of guanine may be followed by up to three subsequent electron transfers, which may eventually enable efficient CpD ring opening when the negative charge resides on the T=T dimer. Consequently, the molecular mechanism of GAT=T self-repair can be envisaged as sequential electron transfer (SET) occurring downhill along the slope of the S-1 potential energy surface. Even though the general features of the SET mechanism are retained in both of the studied stacked conformers, our optimizations of different S-1/S-0 state crossings revealed minor differences which could influence their self-repair efficiencies. We expect that such assessment of the availability and efficiency of the SET process in other DNA oligomers could hint towards other sequences exhibiting similar photochemical properties. Such explorations will be particularly fascinating in the context of the origins of biomolecules on Earth, owing to the lack of external repairing factors in the Archean age.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/GA16-13721S" target="_blank" >GA16-13721S: Víceúrovňové modelování struktury, dynamiky a sbalování DNA.</a><br>

Návaznosti

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

Rok uplatnění

2018

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

—

Svazek periodika

9

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

10

Strana od-do

3131-3140

Kód UT WoS článku

000428987200006

EID výsledku v databázi Scopus

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