RESUMO
Nuclear actin participates in a continuously expanding list of core processes within eukaryotic nuclei, including the maintenance of genomic integrity. In response to DNA damage, nuclear actin polymerises into filaments that are involved in the repair of damaged DNA through incompletely defined mechanisms. We present data to show that the formation of nuclear F-actin in response to genotoxic stress acts as a scaffold for PML NBs and that these filamentous networks are essential for PML NB fission and recruitment of microbodies to DNA lesions. Further to this, we demonstrate that the accumulation of the toxic lamin A precursor prelamin A induces mislocalisation of nuclear actin to the nuclear envelope and prevents the establishment of nucleoplasmic F-actin networks in response to stress. Consequently, PML NB dynamics and recruitment to DNA lesions is ablated, resulting in impaired DNA damage repair. Inhibition of nuclear export of formin mDia2 restores nuclear F-actin formation by augmenting polymerisation of nuclear actin in response to stress and rescues PML NB localisation to sites of DNA repair, leading to reduced levels of DNA damage.
Assuntos
Actinas , Proteínas Nucleares , Actinas/genética , Proteínas Nucleares/genética , Corpos Nucleares da Leucemia Promielocítica , Núcleo Celular , Dano ao DNA , DNA , Proteína da Leucemia Promielocítica/genéticaRESUMO
The common cause of exacerbations in asthmatics are viral infections. Influenza infection especially increases the risk of respiratory exacerbations. The ACIP report puts asthma among indications to regular influenza vaccinations. In practice, many physicians doubt in effectiveness and safety of vaccination in patients suffering from allergy. It caused such procedures were not included in asthma guidelines published by other authors. Our study confirmed the safety of influenza split vaccine vaccination in asthmatics. We proved that vaccination had not any influence on asthma control in 14-day period after injection. We showed also high frequency of, mostly local, side effects. These events were generally mild and transient.