Molecular mechanisms of DNA synthesis by the human replisome

Each time a cell divides, it must duplicate its genome accurately and completely. Genetic inheritance relies on DNA replication, the biochemical process that is responsible for the accurate duplication of our genome and the repair of lesions that might block DNA synthesis or alter the encoded information. We want to understand at molecular level how our cells execute the orderly duplication of the genome and how they cope with DNA damage. We will achieve our goal by working out in atomic detail the shape of the proteins responsible for the duplication process and use this information to explain their mechanism of action. Elucidating the molecular basis of DNA replication is important, because the genomic instability caused by defective replication predisposes to cancer and developmental and neurodegenerative pathologies. Our efforts will advance the molecular understanding of genome biology and our ability to translate such knowledge into medical diagnosis and treatment.