Melanin pigments protect nucleic acid integrity

Melanins are the most abundant skin chromophores. Before being transferred to the target tissues, melanins are synthesized in isolation within melanosomes in melanocytes. Some melanin fragments, however, may leak out of the melanosome. Extramelanosomal melanins interact with nuclear DNA and promote photochemical damage under UV exposure, while DNA-melanin complexes are formed. However, it is unknown how these complexes affect DNA independently of UV, and whether RNA can also form complexes with melanins. Here, we show that DNA-melanin and RNA-melanin complexes are formed under physiological conditions and improve the integrity of the nucleic acids with a high dependency on the melanin form (eumelanin or pheomelanin) involved. After inducing strand shear stress on complexes from chicken follicular melanocytes and comparing them with nucleic acids not bound to melanins, we found that eumelanin protects DNA from strand breaks, while pheomelanin protects RNA. Eumelanin also protects DNA from oxidative damage as revealed by a reduced formation of 8-hydroxy-2'-deoxyguanosine, and both eumelanin and pheomelanin protect RNA from oxidative damage. We provide unprecedented evidence of coexistence of DNA- and RNA-melanin complexes and resolve the long-discussed nature of the interaction as significantly protective. This helps in understanding pigmentation-related diseases and the synthesis of more resistant nucleic acid vectors.