Biological sunscreens and DNA-repair enzymes

Conventional sunscreen intercepts photons before they reach DNA. This category tries to add a second stage — repairing or absorbing what gets through — and the two halves of it fail in different places.

Two wavelength bands, two damage mechanisms

UVB (280–315 nm) is absorbed directly by DNA bases. The characteristic lesions are cyclobutane pyrimidine dimers, in which adjacent thymines or cytosines become covalently joined, and 6-4 photoproducts. Both distort the helix and stall replication and transcription; the mutational signature of skin cancer reflects them directly.

UVA (315–400 nm) is absorbed poorly by DNA and acts mostly indirectly, exciting endogenous chromophores that generate reactive oxygen species, which oxidise guanine to 8-oxo-guanine and attack lipids and proteins. UVA penetrates deeper — into the dermis, where it degrades the collagen and elastin network. It has also been shown to produce cyclobutane dimers by an indirect route, including so-called dark dimers that continue forming for hours after exposure ends, via chemiexcitation involving melanin degradation products.

Humans repair all of this by nucleotide excision repair — recognise the distortion, excise a stretch of about 24–32 nucleotides, resynthesise, ligate. It is a multi-protein, multi-step, ATP-consuming pathway, and its failure modes are severe: the inherited defects underlying xeroderma pigmentosum sit in this pathway.

Photolyase: an enzyme we do not have

Many bacteria, fungi, plants and non-placental animals carry photolyase, a flavoprotein that reverses a pyrimidine dimer in one step. It binds the lesion, and blue light absorbed by its cofactor drives electron transfer into the dimer, splitting the cyclobutane ring and restoring the two bases. It needs no excision and no resynthesis.

Placental mammals lack functional photolyase. Cosmetic products supplying it — typically as an extract of Anabaena or a similar organism, delivered in liposomes — are therefore adding a capability the tissue does not have, which is a genuinely unusual proposition for a topical.

The obstacle is delivery, and it is the same obstacle that limits every large topical active. Photolyase is a protein of roughly 50 kDa; the stratum corneum restricts passive penetration to molecules an order of magnitude smaller, and the enzyme must reach not merely the epidermis but the nucleus of a living keratinocyte to act. Liposomal encapsulation is the standard answer, and the published support rests largely on reduced dimer counts in biopsies rather than on demonstrated nuclear delivery. The mechanism is real and specific; the transport step is the part that carries the uncertainty.

Mycosporine-like amino acids and melanin

MAAs are small cyclohexenone or cyclohexenimine compounds made by cyanobacteria, algae and fungi. They absorb strongly between roughly 310 and 362 nm and are remarkably photostable, because they dissipate the absorbed energy as heat rather than through photochemistry — so they do not generate the radicals that some organic filters do on degradation.

Melanin, particularly eumelanin, is a broadband absorber and a radical scavenger, and in skin it is positioned as supranuclear caps shielding keratinocyte nuclei from above.

Neither is sold as a sunscreen active, and the reason is regulatory rather than scientific. UV filters are governed by positive lists — Annex VI of EU Regulation 1223/2009, the FDA’s OTC sunscreen monograph in the United States — and a substance not on the list may not be used as a filter, however well it absorbs. So these ingredients appear as antioxidants or “actives” alongside listed filters, and a product containing them still gets its SPF from conventional chemistry.