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International Journal of Molecular... Mar 2022Laccases (Lac) and tyrosinases (TYR) are mild oxidants with a great potential in research and industry. In this work, we review recent advances in their use in organic... (Review)
Review
Laccases (Lac) and tyrosinases (TYR) are mild oxidants with a great potential in research and industry. In this work, we review recent advances in their use in organic synthesis. We summarize recent examples of Lac-catalyzed oxidation, homocoupling and heterocoupling, and TYR-catalyzed -hydroxylation of phenols. We highlight the combination of Lac and TYR with other enzymes or chemical catalysts. We also point out the biological and pharmaceutical potential of the products, such as dimers of piceid, lignols, isorhamnetin, rutin, caffeic acid, 4-hydroxychalcones, thiols, hybrid antibiotics, benzimidazoles, benzothiazoles, pyrimidine derivatives, hydroxytyrosols, alkylcatechols, halocatechols, or dihydrocaffeoyl esters, etc. These products include radical scavengers; antibacterial, antiviral, and antitumor compounds; and building blocks for bioactive compounds and drugs. We summarize the available enzyme sources and discuss the scalability of their use in organic synthesis. In conclusion, we assume that the intensive use of laccases and tyrosinases in organic synthesis will yield new bioactive compounds and, in the long-term, reduce the environmental impact of industrial organic chemistry.
Topics: Chemistry Techniques, Synthetic; Laccase; Monophenol Monooxygenase; Oxidation-Reduction; Phenols
PubMed: 35408822
DOI: 10.3390/ijms23073462 -
Scientific Reports Nov 2023In search of novel breast cancer (BC) risk variants, we performed a whole-exome sequencing and variant analysis of 69 Finnish BC patients as well as analysed...
In search of novel breast cancer (BC) risk variants, we performed a whole-exome sequencing and variant analysis of 69 Finnish BC patients as well as analysed loss-of-function variants identified in DNA repair genes in the Finns from the Genome Aggregation Database. Additionally, we carried out a validation study of SERPINA3 c.918-1G>C, recently suggested for BC predisposition. We estimated the frequencies of 41 rare candidate variants in 38 genes by genotyping them in 2482-4101 BC patients and in 1273-3985 controls. We further evaluated all coding variants in the candidate genes in a dataset of 18,786 BC patients and 182,927 controls from FinnGen. None of the variants associated significantly with cancer risk in the primary BC series; however, in the FinnGen data, NTHL1 c.244C>T p.(Gln82Ter) associated with BC with a high risk for homozygous (OR = 44.7 [95% CI 6.90-290], P = 6.7 × 10) and a low risk for heterozygous women (OR = 1.39 [1.18-1.64], P = 7.8 × 10). Furthermore, the results suggested a high risk of colorectal, urinary tract, and basal-cell skin cancer for homozygous individuals, supporting NTHL1 as a recessive multi-tumour susceptibility gene. No significant association with BC risk was detected for SERPINA3 or any other evaluated gene.
Topics: Humans; Female; Genetic Predisposition to Disease; Breast Neoplasms; Heterozygote; Breast; Finland; Deoxyribonuclease (Pyrimidine Dimer)
PubMed: 38036545
DOI: 10.1038/s41598-023-47441-w -
Journal of Biological Rhythms Feb 2020CRYPTOCHROMES (CRYs) are structurally related to ultraviolet (UV)/blue-sensitive DNA repair enzymes called photolyases but lack the ability to repair pyrimidine dimers... (Review)
Review
CRYPTOCHROMES (CRYs) are structurally related to ultraviolet (UV)/blue-sensitive DNA repair enzymes called photolyases but lack the ability to repair pyrimidine dimers generated by UV exposure. First identified in plants, CRYs have proven to be involved in light detection and various light-dependent processes in a broad range of organisms. In , CRY's best understood role is the cell-autonomous synchronization of circadian clocks. However, CRY also contributes to the amplitude of circadian oscillations in a light-independent manner, controls arousal and UV avoidance, influences visual photoreception, and plays a key role in magnetic field detection. Here, we review our current understanding of the mechanisms underlying CRY's various circadian and noncircadian functions in fruit flies.
Topics: Animals; Circadian Clocks; Circadian Rhythm; Cryptochromes; Drosophila; Drosophila Proteins; Light; Photoreceptor Cells, Invertebrate
PubMed: 31599203
DOI: 10.1177/0748730419878290 -
Biomolecules May 2021Genomic integrity is constantly insulted by solar ultraviolet (UV) radiation. Adaptative cellular mechanisms called DNA damage responses comprising DNA repair, cell... (Review)
Review
Genomic integrity is constantly insulted by solar ultraviolet (UV) radiation. Adaptative cellular mechanisms called DNA damage responses comprising DNA repair, cell cycle checkpoint, and apoptosis, are believed to be evolved to limit genomic instability according to the photoperiod during a day. As seen in many other key cellular metabolisms, genome surveillance mechanisms against genotoxic UV radiation are under the control of circadian clock systems, thereby exhibiting daily oscillations in their catalytic activities. Indeed, it has been demonstrated that nucleotide excision repair (NER), the sole DNA repair mechanism correcting UV-induced DNA photolesions, and ataxia-telangiectasia-mutated and Rad3-related (ATR)-mediated cell cycle checkpoint kinase are subjected to the robust control of the circadian clock. The molecular foundation for the circadian rhythm of UV-induced DNA damage responses in mammalian cells will be discussed.
Topics: Animals; Ataxia Telangiectasia Mutated Proteins; Circadian Rhythm; DNA Damage; DNA Repair; Humans; Ultraviolet Rays
PubMed: 34064641
DOI: 10.3390/biom11050715 -
ACS Omega Sep 2022Melanoma is a lethal type of skin tumor that has been linked with sunlight exposure chiefly in fair-skinned human populations. Wavelengths from the sun that can reach... (Review)
Review
Melanoma is a lethal type of skin tumor that has been linked with sunlight exposure chiefly in fair-skinned human populations. Wavelengths from the sun that can reach the earth's surface include UVA radiation (320-400 nm) and UVB radiation (280-320 nm). UVB effectively induces the formation of dimeric DNA photoproducts, preferentially the cyclobutane pyrimidine dimers (CPDs). The characteristic UVB signature mutations in the form of C to T mutations at dipyrimidine sequences are prevalent in melanoma tumor genomes and have been ascribed to deamination of cytosines within CPDs before DNA polymerase bypass. However, evidence from epidemiological, animal, and other experimental studies also suggest that UVA radiation may participate in melanoma formation. The DNA damage relevant for UVA includes specific types of CPDs at TT sequences and perhaps oxidative DNA damage to guanine, both induced by direct or indirect, photosensitization-mediated chemical and biophysical processes. We summarize the evidence for a potential role of UVA in melanoma and discuss some of the mechanistic pathways of how UVA may induce mutagenesis in melanocytes.
PubMed: 36157735
DOI: 10.1021/acsomega.2c04424 -
Photochemistry and Photobiology Mar 2023Light is one way to excite an electron in biology. Another is chemiexcitation, birthing a reaction product in an electronically excited state rather than exciting from... (Review)
Review
Light is one way to excite an electron in biology. Another is chemiexcitation, birthing a reaction product in an electronically excited state rather than exciting from the ground state. Chemiexcited molecules, as in bioluminescence, can release more energy than ATP. Excited states also allow bond rearrangements forbidden in ground states. Molecules with low-lying unoccupied orbitals, abundant in biology, are particularly susceptible. In mammals, chemiexcitation was discovered to transfer energy from excited melanin, neurotransmitters, or hormones to DNA, creating the lethal and carcinogenic cyclobutane pyrimidine dimer. That process was initiated by nitric oxide and superoxide, radicals triggered by ultraviolet light or inflammation. Several poorly understood chronic diseases share two properties: inflammation generates those radicals across the tissue, and cells that die are those containing melanin or neuromelanin. Chemiexcitation may therefore be a pathogenic event in noise- and drug-induced deafness, Parkinson's disease, and Alzheimer's; it may prevent macular degeneration early in life but turn pathogenic later. Beneficial evolutionary selection for excitable biomolecules may thus have conferred an Achilles heel. This review of recent findings on chemiexcitation in mammalian cells also describes the underlying physics, biochemistry, and potential pathogenesis, with the goal of making this interdisciplinary phenomenon accessible to researchers within each field.
Topics: Animals; Melanins; Photochemistry; Pyrimidine Dimers; Ultraviolet Rays; Mammals
PubMed: 36681894
DOI: 10.1111/php.13781 -
Journal of the European Academy of... Jul 2024This review aimed at summarizing some of the key points that were discussed during the photoprotection session at the International Forum of Dermatology in 2022. This... (Review)
Review
This review aimed at summarizing some of the key points that were discussed during the photoprotection session at the International Forum of Dermatology in 2022. This international conference was designed to address prominent topics of clinical dermatology in a holistic way, allowing to articulate multiple viewpoints. Therefore, this review does not claim to be exhaustive, but is instead intended to give an overview of recent developments and ongoing controversies in the field of photoprotection. Cumulative ultraviolet radiation (UVR) exposure is the major aetiological factor in the development of photoageing, photoimunosuppression and photocarcinogenesis. UVA (320-400 nm) penetrates into the dermis and damages DNA and other intracellular and acellular targets primarily by generating reactive oxygen species (ROS). It is the major contributor to photoageing, characterized by fine and coarse wrinkles, dyspigmentation and loss of elasticity. UVB (290-320 nm) is responsible for sunburns through direct damage to DNA by the formation of 6-4 cyclobutane pyrimidine dimers (CPDs) and pyrimidine 6-4 pyrimidone photoproducts. Both UVA and UVB exposure increase the risk of basal cell carcinoma, squamous cell carcinoma and melanoma. In recent years, visible light (VL; 400-700 nm) has also been implicated in the exacerbation of conditions aggravated by sun exposure such as hyperpigmentation and melasma. Photoprotection is a critical health strategy to reduce the deleterious effects of UVR and VL. Comprehensive photoprotection strategies include staying in the shade when outdoors, wearing photoprotective clothing including a wide-brimmed hat, and sunglasses, and the use of sunscreen. Due to the absorption of UV filters, the safety of sunscreens has been questioned. Newer sunscreens are becoming available with filters with absorption even beyond the UV spectrum, offering enhanced protection compared with older products. Prevention of photocarcinogenesis, sun-induced or sunlight-exacerbated hyperpigmentary conditions and drug-induced photosensitivity is an important reason for adopting comprehensive photoprotection strategies.
Topics: Humans; Sunscreening Agents; Ultraviolet Rays; Skin Aging; Skin Neoplasms; Sunburn
PubMed: 38924160
DOI: 10.1111/jdv.19677 -
Biophysical Reviews Aug 2022DNA glycosylases are DNA repair enzymes capable of removing damaged nitrogenous bases, including those formed as a result of UV irradiation with sunlight (approximately... (Review)
Review
UNLABELLED
DNA glycosylases are DNA repair enzymes capable of removing damaged nitrogenous bases, including those formed as a result of UV irradiation with sunlight (approximately 300-400 нм). DNA glycosylases are common not only among bacteria, archaea, and eukaryotes, but some groups of viruses can also encode them. The best-known viral glycosylase is endonuclease V (DenV, Pdg-T4) of Escherichia virus T4, the main substrate of which is cyclobutane pyrimidine dimers. DenV is isolated separately from other large families of glycosylases; it is quite common in nature and has homologs in a number of other viruses and even bacteria. However, the ways of its origin are poorly understood. The best-known DenV homolog is the glycosylase of Chlorella virus strain, PBCV-1 (Cv-pdg). This review contains the main known data on the structure and mechanism of operation of DenV and its homologs. The issues of biological importance and distribution of the enzyme and its homologs among viruses are considered and supplemented separately.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s12551-022-00972-4.
PubMed: 36124272
DOI: 10.1007/s12551-022-00972-4 -
Antioxidants (Basel, Switzerland) Feb 2022UV-like DNA damage is created in the dark by chemiexcitation, in which UV-activated enzymes generate reactive oxygen and nitrogen species that create a dioxetane on...
UV-like DNA damage is created in the dark by chemiexcitation, in which UV-activated enzymes generate reactive oxygen and nitrogen species that create a dioxetane on melanin. Thermal cleavage creates an electronically excited triplet-state carbonyl whose high energy transfers to DNA. Screening natural compounds for the ability to quench this energy identified polyenes, polyphenols, mycosporine-like amino acids, and related compounds better known as antioxidants. To eliminate false positives such as ROS and RNS scavengers, we then used the generator of triplet-state acetone, tetramethyl-1,2-dioxetane (TMD), to excite the triplet-energy reporter 9,10-dibromoanthracene-2-sulfonate (DBAS). Quenching measured as reduction in DBAS luminescence revealed three clusters of 50% inhibitory concentration, ~50 μM, 200-500 μM, and >600 μM, with the former including sorbate, ferulic acid, and resveratrol. Representative triplet-state quenchers prevented chemiexcitation-induced "dark" cyclobutane pyrimidine dimers (dCPD) in DNA and in UVA-irradiated melanocytes. We conclude that (i) the delocalized pi electron cloud that stabilizes the electron-donating activity of many common antioxidants allows the same molecule to prevent an electronically excited species from transferring its triplet-state energy to targets such as DNA and (ii) the most effective class of triplet-state quenchers appear to operate by energy diversion instead of electron donation and dissipate that energy by isomerization.
PubMed: 35204239
DOI: 10.3390/antiox11020357 -
Genes Jul 2021The nucleotide excision repair (NER) is essential for the repair of ultraviolet (UV)-induced DNA damage, such as cyclobutane pyrimidine dimers (CPDs) and... (Review)
Review
The nucleotide excision repair (NER) is essential for the repair of ultraviolet (UV)-induced DNA damage, such as cyclobutane pyrimidine dimers (CPDs) and 6,4-pyrimidine-pyrimidone dimers (6,4-PPs). Alterations in genes of the NER can lead to DNA damage repair disorders such as Xeroderma pigmentosum (XP). XP is a rare autosomal recessive genetic disorder associated with UV-sensitivity and early onset of skin cancer. Recently, extensive research has been conducted on the functional relevance of splice variants and their relation to cancer. Here, we focus on the functional relevance of alternative splice variants of XP genes.
Topics: DNA Damage; DNA Repair; Humans; Mutation; Pyrimidine Dimers; RNA Splicing; Xeroderma Pigmentosum
PubMed: 34440347
DOI: 10.3390/genes12081173