title: Nuclear envelope defects impede a proper response to micronuclear DNA lesions.
abstract: When damage is inflicted in nuclear DNA, cells activate a hierarchical plethora of proteins that constitute the DNA damage response machinery. In contrast to the cell nucleus, the ability of micronuclear DNA lesions to activate this complex network is controversial. In order to determine whether the DNA contained in micronuclei is protected by the cellular damage response system, we studied the recruitment of excision repair factors to photolesions inflicted in the DNA of radiation-induced micronuclei. To perform this analysis, primary human dermal fibroblasts were exposed to UV-C light to induce photolesions in nuclear and micronuclear DNA. By means of immunofluorescence techniques, we observed that most micronuclei were devoid of NER factors. We conclude that UV photoproducts in micronuclei are mostly unable to generate an effective DNA damage response. We observed that the micronuclear envelope structure is a determinant factor that influences the repair of the DNA lesions inside micronuclei. Therefore, our results allow us to conclude that photolesions in radiation-induced micronuclei are poorly processed because the repair factors are unable to reach the micronuclear chromatin when a micronucleus is formed or after a genotoxic insult.
authors.affiliation: Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: Mariona
authors.initials: M
authors.lastname: Terradas
authors.forename: Marta
authors.initials: M
authors.lastname: Martín
authors.forename: Laia
authors.initials: L
authors.lastname: Hernández
authors.forename: Laura
authors.initials: L
authors.lastname: Tusell
authors.forename: Anna
authors.initials: A
authors.lastname: Genescà
mesh_terms: D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D002478:Cells, Cultured; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage / Q000528:radiation effects*; D004260:DNA Repair / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005720:Gamma Rays; D006801:Humans; D009685:Nuclear Envelope / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D012867:Skin / Q000166:cytology; D014466:Ultraviolet Rays
chemical_list: D002843:Chromatin; D004247:DNA