Seminar Abstract: The integrity of the DNA replication process is intimately linked with maintaining genome stability. However, it is not clear whether core components of the replisome are directly involved in stabilising and protecting damaged forks. This talk will provide evidence indicating that the replisome component DONSON functions as a molecular conduit between the replication machinery and the HR-dependent fork stability pathway.

Biosketch: For over two decades, research from the Stewart laboratory has focused on understanding of how germline mutations in genes that preserve genomic integrity cause paediatric neurodegenerative and neurodevelopmental disorders. The Stewart laboratory combines human genetics and cell biology approaches to define disease mechanisms at the molecular level underlying a diverse range of genome instability disorders. Alongside this, the Stewart laboratory combines cell-based functional assays with genetics to enhance the molecular diagnostics for these orphan genetic diseases, which has helped to establish the University of Birmingham as a nationally recognised referral centre for the confirmation of genetic diagnosis of Ataxia-Telangiectasia (A-T) and A-T-like disorders. The Stewart laboratory continues to provide cellular and genetic diagnostics to both UK and international patients, which is vital for informing genetic counselling and directing appropriate clinical management of specific chromosomal instability disorders. Furthermore, this combinatorial scientific research approach has led to the identification of a substantial number of new human disease genes, several of which (e.g. RNF168, TRAIP and DONSON) the Stewart laboratory has demonstrated to encode entirely novel genome stability maintenance factors. The identification of these factors has not only significantly increased our scientific knowledge of the fundamental cellular pathways dysregulated in human neurodevelopmental disorders but has also provided insight into those pathways that are compromised in cancer cells or following viral infection.