Light-driven DNA repair by photolyases
Open accessAbstract
DNA photolyases are highly efficient light-driven DNA repair enzymes which revert the genome-damaging effects caused by ultraviolet (UV) radiation. These enzymes occur in almost all living organisms exposed to sunlight, the only exception being placental mammals like humans and mice. Their catalytic mechanism employs the light-driven injection of an electron onto the DNA lesion to trigger the cleavage of cyclobutane- pyrimidine dimers or 6-4 photoproducts inside duplex DNA. Spectroscopic and structural analysis has recently yielded a concise view of how photolyases recognize these DNA lesions involving two neighboring bases, catalyze the repair reaction within a nanosecond and still achieve quantum efficiencies of close to one. Apart from these mechanistic aspects, the potential of DNA photolyases for the generation of highly UV-resistant organisms, or for skin cancer prevention by ectopical application is increasingly recognized.
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DNA photolyases are monomeric flavin-dependent repair enzymes of 45-66 kDa with 420-616 amino acid residues and two known cofactors, one catalytic and one light-harvesting.
“DNA photolyases (45–66 kDa) having 420–616 amino acid residues [158] are monomeric flavin-dependent repair enzymes, consisting of two known cofactors, a catalytic cofactor and a light-harvesting cofactor.”
From Molecular Mechanisms of Ultraviolet Radiation‐Induced DNA Damage and Repair (2010) · cites this paper as [158]
Photolyase binds specifically to CPDs or 6-4PPs and directly monomerizes the cyclobutane ring of the pyrimidine dimer using visible or blue light, protecting the genome from UVR damage.
“The enzyme binds specifically to the CPDs (CPD photolyase) or 6-4PPs (6-4 photolyase) and directly monomerizes the cyclobutane ring of the pyr <> pyr, using the energy of visible/blue-light and protects the genome from deleterious effects of UVR [157, 158].”
From Molecular Mechanisms of Ultraviolet Radiation‐Induced DNA Damage and Repair (2010) · cites this paper as [158]
In the absence of blue light, photolyases bind to CPDs and 6-4PPs.
“In the absence of blue light photolyases bind to CPDs, and 6-4PPs.”
From Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies (2020) · cites this paper as [81]
Energy obtained through excitation of the chromophore is transferred to FADH, and photoexcited FADH provides energy for dimer-splitting.
“The energy obtained through excitation of chormophore is then transferred to important cofactor—reduced flavin adenine dinucleotide (FADH). Consequently, photoexcitated FADH provides energy for the dimer-splitting.”
From Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies (2020) · cites this paper as [81]
CPDs and 6-4PPs are the two main types of photolesions repaired by photolyases.
“CPDs and 6-4PPs are the two main types of photolesions repaired by photolyases.”
From Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies (2020) · cites this paper as [81]
A thymine pair is flipped back into the DNA duplex, and the hydrogen bond between thymine and adenine is formed.
“A thymine pair is consequently flipped back into the DNA duplex and the hydrogen bond between thymine and adenine is formed.”
From Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies (2020) · cites this paper as [81]
Subsequent back electron transfer regenerates FADH, ensuring the proper FAD form for the next reaction.
“Subsequent back electron transfer regenerates the FADH, ensuring the proper FAD form for the next reaction.”
From Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies (2020) · cites this paper as [81]
Placental mammals, including humans, lack photolyase activity, and repair of UV-induced damage is probably replaced by NER.
“Placental mammals (including humans) lack photolyase activity, and the repair of UV-induced damage is probably replaced by the activity of NER.”
From Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies (2020) · cites this paper as [81]
In many organisms, photolyases are the key enzymes that remove photo-damage.
“However, in many organisms, photolyases are the key enzymes that remove photo-damage.”
From Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies (2020) · cites this paper as [81]
Absorption of light by the class-specific chromophore leads to its excitation.
“The absorption of light by the class specific chromophore (either 5,10-methyl tetrahydrofolate (MTHF) or 8-hydroxy-5-deazaflavin (8-HDF)) leads to its excitation.”
From Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies (2020) · cites this paper as [81]
Two classes of CPD photolyases with different electron transfer pathways and different mechanistic properties exist.
“Two classes of CPD photolyases with different pathway of electron transfer, and different mechanistic properties exist.”
From Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies (2020) · cites this paper as [81]
Conflicting results exist on oxetane formation during repair.
“However, conflicting results exist on the oxetane formation during repair.”
From Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies (2020) · cites this paper as [81]
Covalent links between adjacent pyrimidines in dimers are broken, and proper DNA structure is restored.
“Again, the covalent links between adjacent pyrimidines in the dimers are broken, and the proper structure of DNA molecule is restored [77,78,79,80,81].”
From Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies (2020) · cites this paper as [81]
Repair of 6-4PPs is different than CPDs and requires (6-4PP) photolyase and involves oxetane intermediate formation.
“The repair of 6-4PPs is different than CPDs and requires (6-4PPs) photolyase and involves oxetane intermediate formation.”
From Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies (2020) · cites this paper as [81]
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Molecular Mechanisms of Ultraviolet Radiation‐Induced DNA Damage and Repair
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“The exposure of UVR, IR, and certain genotoxic chemicals may result in single as well as double DNA strand breaks.”
BackgroundInfluentialFocus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies
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- Authors
- Essen, L. O., & Klar, T.
- Affiliations
- Philipps University of Marburg (DE)
- Corresponding author
- Essen, L. O.
- ORCID
- Essen, L. O.
- Venue
- Cellular and Molecular Life Sciences
- Published
- 2006-05-15
- Volume
- 63
- Issue
- 11
- Pages
- 1266-1277
- ISSN
- 1420-682X (ISSN-L)
- 1420-9071
- PMC
- PMC11136382
- OpenAlex
- W2029277210
- Cited by
- 200
- References
- 70
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 9 · 2023: 9 · 2022: 9 · 2021: 13 · 2020: 15 · 2019: 3 · 2018: 10 · 2017: 9 · 2016: 16 · 2015: 10 · 2014: 12 · 2013: 14 · 2012: 8
- FWCI
- 3.81
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cellular and Molecular Life Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Physical Sciences › Chemistry › Physical and Theoretical Chemistry › Photochemistry and Electron Transfer Studies
- Keywords
- DNA photolyase, ultraviolet radiation, cyclobutane pyrimidine dimers, 6-4 photoproducts, electron injection, photoreactivation, DNA damage recognition, repair mechanisms, quantum efficiency, UV resistance, skin cancer prevention
- MeSH terms
- Animals, DNA, Deoxyribodipyrimidine Photo-Lyase, DNA Repair, Forecasting, Humans, Light, Models, Biological, Models, Molecular, Pyrimidine Dimers, Skin Neoplasms, Ultraviolet Rays
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