BIT by BIT: Associating Transcription to Ageing

• Autor(a) principal: Teixeira, Ian Lopes
• Data de Publicação: 2023
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10362/161478
• topic: Ageing; Double-strand break; Break-Induced Transcription; Spurious transcription; Domínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e Tecnologias

A common and longstanding view of the ageing process poses that the onset of ageing hallmarks is driven by the gain of somatic mutations deriving from the inaccurate repair of DNA lesions, the most catastrophic of which is Double-strand Break (DSB). However, compelling evidence accumulated during the last decade demonstrated that, in addition to causing mutations, DSBs can initiate gene expression events. Using live-cell imaging, it was recently provided direct evidence of transcription initiation at DSB sites, a process dubbed Break-Induced Transcription (BIT), which was previously reported as an important step of DSB repair and gene expression regulation. A trademark of the ageing cell is the widespread rewiring of gene expression, including an increase in spurious transcription. This led us to propose the disruptive hypothesis that alternative gene expression events established through BIT at DSB contribute to the establishment of the ageing phenotype. By using public human data from genome-wide detection techniques of DSB (BLISS, DSBCapture, Break-seq) and high-throughput sequencing (RNA-seq), whose cells under- went no treatment, it was possible to identify natural BIT events at the whole genome level. We were able to develop a genome-wide detection tool of BIT independently of the DSB technique resolution. The available dataset provided no evidence of BIT events influencing ageing itself.