Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies

Kciuk, Mateusz; Marciniak, Beata; Kontek, Renata

doi:10.3390/ijms21197264

Cited by 75 publications

(52 citation statements)

References 185 publications

(265 reference statements)

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“…DNA is the most abundant chromophore present in the epidermis, UVB is directly absorbed by DNA which causes molecular rearrangements forming the photoproducts such as CPD and 6–4 photoproducts ( D'Orazio et al, 2013 ; Chen et al, 2014 ). CPDs are the main DNA damage lesions responsible for cell death following UV exposure ( Kciuk and Marciniak 2020 ). Increased formation of CPD can lead to an increase in the phosphorylation of the histone protein H2AX at Ser139.…”

Section: Discussionmentioning

confidence: 99%

Keratinocyte Growth Factor 2 Ameliorates UVB-Induced Skin Damage via Activating the AhR/Nrf2 Signaling Pathway

et al. 2021

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Objective: Exposure to ultraviolet B (UVB) can cause skin damage through oxidative stress, DNA damage, and apoptosis. Keratinocyte growth factor (KGF) has been shown to reduce the content of intracellular reactive oxygen species (ROS) following UVB exposure, a role that is crucial for the efficient photoprotection of skin. The present study evaluated the photoprotective effect of KGF-2 on UVB-induced skin damage and explored its potential molecular mechanism.Methods: To evaluate the effect of KGF-2 on UVB-induced damage ex vivo, a human epidermal full-thickness skin equivalent was pretreated without or with KGF-2 and then exposed to UVB and the levels of histopathological changes, DNA damage, inflammation, and apoptosis were then evaluated. The ability of KGF-2 to protect the cells against UVB-inflicted damage and its effect on ROS production, apoptosis, and mitochondrial dysfunction were determined in HaCaT cells.Results: Pretreatment of the epidermis with KGF-2 ameliorated the extent of photodamage. At the cellular level, KGF-2 could attenuate ROS production, apoptosis, DNA damage, and mitochondrial dysfunction caused by UVB exposure. KGF-2 could also activate the aryl hydrocarbon receptor (AhR) to trigger the Nrf2 signaling pathway.Conclusion: Taken together, our findings suggested that KGF-2 could ameliorate UVB-induced skin damage through inhibiting apoptosis, reducing oxidative stress, and preventing DNA damage and mitochondrial dysfunction via regulating AhR/Nrf2 signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Keratinocyte Growth Factor 2 Ameliorates UVB-Induced Skin Damage via Activating the AhR/Nrf2 Signaling Pathway

et al. 2021

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“…Exposed to UV radiation, DNA can become damaged where photochemical reactions allow for two adjacent pyrimidine base pairs, prevalently at TpT, TpC, and CpT dyads, to cross link together, forming a pyrimidine dimer (71). Such lesions, if not repaired, may then become the reason for mutations and UV-caused skin cancers (72). There are two major classes of UV-induced DNA lesions (Figure 2A): pyrimidine-pyrimidone (6-4) photoproduct (PP), and cyclobutane pyrimidine dimers (CPDs).…”

Section: Uv-caused Damage At Pyrimidine Dyadsmentioning

confidence: 99%

Structure-driven effects on genomic DNA damage propensity at G-quadruplex sites

Abdullah

Feng

Pflughaupt

et al. 2021

Preprint

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Our genome contains about half a million sites capable of forming G-quadruplex (G4) structures. Such structural formations, often localised at important regulatory loci, have high capability of altering the predisposition of corresponding genomic spans to endogenous and exogenous DNA damage. In this work, we devised an approach to systematically enrich and zoom onto structure-driven effects on the propensity to undergo 9 types of DNA damage: ultraviolet radiation-induced pyrimidine-pyrimidone (6-4) photoproduct PP and cyclobutane pyrimidine dimer CPD couplings (two dyad-based subtypes in each), cisplatin-mediated G-G crosslinks, reactive oxygen species induced 8-oxoguanine damage, DNA fragmentation upon natural decay and fossilisation, breakages from artificial enzymatic cleavage and ultrasound sonication. Our results indicate that the structural effects on DNA damageability at G4 sites are not a simple combination of shielding (G4 strand) and de-shielding (opposite strand) against damaging factors, and the outcomes have different patterns and variation from one damage type to another, highly dependent on the G4 strength and relative strand localisation. The results are accompanied by electronic structure calculations, detailed structural parallels and considerations.

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“…Recent reports suggest that they are released inside short oligonucleotides (30 mer) in a tight complex with the Transcription Factor II Human (TFIIH) and Replication Protein A (RPA) [9,13]. These oligonucleotides undergo a limited degree of degradation and can activate Mitogen-Activated Protein Kinase (MAPK) and checkpoint pathways involving tumor protein 53 (p53), Cyclin Dependent Kinases (CDK) inhibitor factor and p21, respectively, for the prevention of UV-damage, or in alternative, apoptosis [14]. In addition, they stabilize human Topoisomerase 1 (TOP1), affecting transcription bubble and replication fork [15].…”

Section: Introductionmentioning

confidence: 99%

Lignin Nanoparticles Deliver Novel Thymine Biomimetic Photo-Adducts with Antimelanoma Activity

Gabellone

Piccinino

Filippi

et al. 2022

IJMS

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We report here the synthesis of novel thymine biomimetic photo-adducts bearing an alkane spacer between nucleobases and characterized by antimelanoma activity against two mutated cancer cell lines overexpressing human Topoisomerase 1 (TOP1), namely SKMEL28 and RPMI7951. Among them, Dewar Valence photo-adducts showed a selectivity index higher than the corresponding pyrimidine-(6-4)-pyrimidone and cyclobutane counterpart and were characterized by the highest affinity towards TOP1/DNA complex as evaluated by molecular docking analysis. The antimelanoma activity of novel photo-adducts was retained after loading into UV photo-protective lignin nanoparticles as stabilizing agent and efficient drug delivery system. Overall, these results support a combined antimelanoma and UV sunscreen strategy involving the use of photo-protective lignin nanoparticles for the controlled release of thymine dimers on the skin followed by their sacrificial transformation into photo-adducts and successive inhibition of melanoma and alert of cellular UV machinery repair pathways.

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Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies

Cited by 75 publications

References 185 publications

Keratinocyte Growth Factor 2 Ameliorates UVB-Induced Skin Damage via Activating the AhR/Nrf2 Signaling Pathway

Keratinocyte Growth Factor 2 Ameliorates UVB-Induced Skin Damage via Activating the AhR/Nrf2 Signaling Pathway

Structure-driven effects on genomic DNA damage propensity at G-quadruplex sites

Lignin Nanoparticles Deliver Novel Thymine Biomimetic Photo-Adducts with Antimelanoma Activity

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