Role of CSA and CSB proteins in cytokinesis ; Ruolo delle proteine CSA e CSB nella citodieresi

Dottorato di ricerca in Genetica e biologia cellulare ; Cockayne syndrome (CS) is a genetic disease inherited in an autosomal recessive pattern. CS patients are characterized by photosensitivity, severe growth retardation, cachectic dwarfism, feature of premature aging and progressive neurological abnormalities of the central nervous system including microcephaly, cerebellar atrophy and demyelinating peripheral neuropathy. The average life span of children with this syndrome is about 12 years of age. CS patients have been assigned to two genetic complementation groups (CS-A and CS-B), whose corresponding genes (csa and csb) have been cloned and characterized (Henning et al 1995; Troelstra et al., 1992; Lehmann, 1982). CSA and CSB proteins have critical roles in a sub pathway of nucleotide excision repair known as transcription-coupled repair (TCR). Although a defect in TCR pathway could potentially account for the enhanced photosensitivity of CS patients, other pathological features including neurological dysfunctions may not solely explained by a DNA repair defect and requires additional explanations. Accordingly, in the last years it has been suggested that CSA and CSB proteins play multiple pleiotropic functions. More recently, we and others have demonstrated that CSB mediates the transcriptional programs following exposure to cellular stressors such as UV, oxidative damage, inflammation and hypoxia. Therefore, abnormalities in the regulation of RNA pol I and II mediated transcription might provide plausible explanations for many of the somatic features, including aspects of neurological symptoms associated with CS. Observation of neurological symptoms detected either at birth or during early childhood raises the possibility that CSB may have a crucial role in the transcriptional programs that govern the plasticity and the maintenance of the central nervous system during (perinatal and postnatal) pediatric life. Our recent studies showed that CSB suppression affects the neuronal differentiation capability of ...