Lien vers Pubmed [PMID] – 41398050
Lien DOI – 10.1038/s41556-025-01817-4
Nat Cell Biol 2025 Dec; ():
Melanin pigments block genotoxic agents by positioning on the sun-exposed side of the nucleus in human skin keratinocytes. How this positioning is regulated and its role in genome photoprotection remain unknown. Here, by developing a model of human keratinocytes internalizing extracellular melanin into pigment organelles, we show that keratin 5 and keratin 14 intermediate filaments and microtubules control the three-dimensional perinuclear position of pigments, shielding DNA from photodamage. Imaging and microrheology in a human-disease-related model identify structural keratin cages surrounding pigment organelles to stiffen their microenvironment and maintain their three-dimensional position. Optimum supranuclear spatialization of pigment organelles is required for DNA photoprotection and relies on intermediate filaments and microtubules bridged by plectin cytolinkers. Thus, the mechanically driven proximity of pigment organelles to the nucleus is a key photoprotective parameter. Uncovering how human skin counteracts solar radiation by positioning the melanin microparasol next to the genome anticipates that dynamic spatialization of organelles is a physiological response to ultraviolet stress.