Photoinduced intersystem crossing in DNA oxidative lesions and epigenetic intermediates

Francés‐Monerris, Antonio; Lineros‐Rosa, Mauricio; Miranda, Miguel A.; Lhiaubet‐Vallet, Virginie; Monari, Antonio

doi:10.1039/d0cc01132k

Cited by 33 publications

(39 citation statements)

References 49 publications

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“…The latter is a gateway state to a triplet state formed with an approximately 70 % quantum yield. [6][7] Effective triplet-triplet energy transfer [8] has also been documented for 5fdCyd. Therefore, 5fdCyd has the potential to be an internal triplet photosensitizer which can initiate DNA photolesions.…”

Section: Introductionmentioning

confidence: 91%

“…Prior transient absorption experiments on 5fdCyd revealed that the bright 1 ππ* state decays to a dark 1 nπ* state (located on the formyl group) on an ultrafast time scale in acetonitrile (ACN). The latter is a gateway state to a triplet state formed with an approximately 70 % quantum yield [6–7] . Effective triplet‐triplet energy transfer [8] has also been documented for 5fdCyd.…”

Section: Introductionmentioning

confidence: 93%

“…The isosbestic point between the first and second EADS indicates that in ACN the 1 nπ* acts as gateway state for the population of the T 1 3 ππ* triplet state in line with conclusions from the literature. [6][7] However, the ground state bleach kinetics suggests that the 24 ps component should also contain signal from a minor decay channel to the ground state (see below).…”

Section: Distinct Isc Channels For 5fdcyd In Water Versus Acnmentioning

confidence: 99%

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Solvent‐Dependent Stabilization of a Charge Transfer State is the Key to Ultrafast Triplet State Formation in an Epigenetic DNA Nucleoside

Wang

Martínez‐Fernández

Zhang

et al. 2021

Chemistry A European J

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2'-Deoxy-5-formylcytidine (5fdCyd), a naturally occurring nucleoside found in mammalian DNA and mitochondrial RNA, exhibits important epigenetic functionality in biological processes. Because it efficiently generates triplet excited states, it is an endogenous photosensitizer capable of damaging DNA, but the intersystem crossing (ISC) mechanism responsible for ultrafast triplet state generation is poorly understood. In this study, time-resolved mid-IR spectroscopy and quantum mechanical calculations reveal the distinct ultrafast ISC mechanisms of 5fdCyd in water versus acetonitrile. Our experiment indicates that in water, ISC to triplet states occurs within 1 ps after 285 nm excitation. PCM-TD-DFT computations suggest that this ultrafast ISC is mediated by a singlet state with significant cytosine-to-formyl charge-transfer (CT) character. In contrast, ISC in acetonitrile proceeds via a dark 1 nπ* state with a lifetime of~3 ps. CTinduced ISC is not favored in acetonitrile because reaching the minimum of the gateway CT state is hampered by intramolecular hydrogen bonding, which enforces planarity between the aldehyde group and the aromatic group. Our study provides a comprehensive picture of the non-radiative decay of 5fdCyd in solution and new insights into the factors governing ISC in biomolecules. We propose that the intramolecular CT state observed here is a key to the excited-state dynamics of epigenetic nucleosides with modified exocyclic functional groups, paving the way to study their effects in DNA strands.

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Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 93%

Section: Distinct Isc Channels For 5fdcyd In Water Versus Acnmentioning

confidence: 99%

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Solvent‐Dependent Stabilization of a Charge Transfer State is the Key to Ultrafast Triplet State Formation in an Epigenetic DNA Nucleoside

Wang

Martínez‐Fernández

Zhang

et al. 2021

Chemistry A European J

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“…30 Recently, the role of oxidative lesions, namely 5-formyluracil (ForU) 31 and 5-formylcytosine (ForC) 32,33 (see Scheme 1), as potential Trojan Horses has been studied through experiments 34 and theoretical calculations. [35][36][37] It has indeed been recognized, both in model systems and in DNA oligomers, that the inclusion of ForU is correlated with a significant increase in the yield of CPD damages. 34 Furthermore, molecular modeling and simulations have shown that ForU is prone to a facile ISC, leading to an energetically favorable TTET to thymine and that those conditions are maintained in the B-DNA environment.…”

Section: Introductionmentioning

confidence: 99%

“…35 Subsequently, it was shown that ISC is also possible in the case of ForC, even if non-adiabatic molecular dynamics have pointed out a less-favorable phenomenon as compared to ForU. 37 The behavior of ForC in comparison with ForU is indeed extremely intriguing, not only from a photophysical perspective, but also due to its biological relevance. ForC can be considered an oxidative lesion, but also an epigenetic intermediate in the demethylation process of 5-methyl-cytosine (5MetC).…”

Section: Introductionmentioning

confidence: 99%

Thymine Dimerization Induced by Oxidative DNA Lesions and Epigenetic Intermediates via Triplet-Triplet Energy Transfer

Lineros‐Rosa¹,

Francés‐Monerris²,

Monari

et al. 2020

Preprint

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Interaction of nucleic acids with light is a scientific question of paramount relevance not only in the understanding of life functioning and evolution, but also in the insurgence of diseases such as malignant skin cancer and in the development of biomarkers and novel light-assisted therapeutic tools. This work shows that the UVA portion of sunlight, not absorbed by canonical DNA nucleobases, can be absorbed by 5-formyluracil (ForU) and 5-formylcytosine (ForC), two ubiquitous oxidative lesions and epigenetic intermediates present in living beings in natural conditions. We measure the strong propensity of these molecules to populate triplet excited states able to transfer the excitation energy to thymine-thymine dyads, inducing the formation of the highly toxic and mutagenic cyclobutane pyrimidine dimers (CPDs). By using steady-state and transient absorption spectroscopy, NMR, HPLC, and theoretical calculations, we quantify the differences in the triplet-triplet energy transfer mediated by ForU and ForC, revealing that the former is much more efficient in delivering the excitation energy and producing the CPD photoproduct. Although significantly slower than ForU, ForC is also able to harm DNA nucleobases and therefore this process has to be taken into account as a viable photosensitization mechanism. The present findings evidence a rich photochemistry crucial to understand DNA photodamage and of potential use in the development of biomarkers and non-conventional photodynamic therapy agents.

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Remote Photodamaging of DNA by Photoinduced Energy Transport

Wagenknecht

2021

ChemBioChem

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Local DNA photodamaging by light is well-studied and leads to a number of structurally identified direct damage, in particular cyclobutane pyrimidine dimers, and indirect oxidatively generated damage, such as 8-oxo-7,8-hydroxyguanine. Similar damages have now been found at remote sites, at least more than 105 Å (30 base pairs) away from the site of photoexcitation. In contrast to the established mechanisms of local DNA photodamaging, the processes of remote photodamage are only partially understood. Known pathways include those to remote oxidatively generated DNA photodamages, which were elucidated by studying electron hole transport through the DNA about 20 years ago. Recent studies with DNA photosensitizers and mechanistic proposals on photoinduced DNA-mediated energy transport are summarized in this minireview. These new mechanisms to a new type of remote DNA photodamaging provide an important extension to our general understanding to light-induced DNA damage and their mutations.

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Photoinduced intersystem crossing in DNA oxidative lesions and epigenetic intermediates

Abstract: The propensity of 5-formyluracil and 5-formylcytosine, i.e. oxidative lesions and epigenetic intermediates, in acting as intrinsic DNA photosensitizers is unraveled by using a combination of molecular modeling, simulation and spectroscopy.

Cited by 33 publications

References 49 publications

Solvent‐Dependent Stabilization of a Charge Transfer State is the Key to Ultrafast Triplet State Formation in an Epigenetic DNA Nucleoside

Solvent‐Dependent Stabilization of a Charge Transfer State is the Key to Ultrafast Triplet State Formation in an Epigenetic DNA Nucleoside

Thymine Dimerization Induced by Oxidative DNA Lesions and Epigenetic Intermediates via Triplet-Triplet Energy Transfer

Remote Photodamaging of DNA by Photoinduced Energy Transport

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