Jan 12, 2016
| Carolyn Hoff Lynch Room Title: Molecular mechanisms for initiating DNA replication in eukaryotes Abstract:Cellular organisms must replicate their DNA in a timely and accurate manner to preserve gene copy number, chromosome ploidy, and genome stability. In eukaryotes, DNA replication is initiated at specific sites throughout the genome, termed replication origins, which are bound by a multi-subunit protein assembly, the origin recognition complex (ORC). Aided by accessory factors, ORC facilitates loading of the replicative helicase core onto DNA to “license” origins for subsequent DNA replication. In my seminar, I will describe how we used single-particle electron microscopy and X-ray crystallography to gain molecular insights into how the ORC subunits co-assemble, how ORC engages origin DNA, and how ORC interacts with partner proteins. I will discuss structure-guided models for how ORC operates during replicative helicase loading, as well as a novel mechanism for controlling metazoan ORC activity that may help regulate the onset of DNA replication in vivo. In addition, I will highlight how mutations in ORC subunits link ORC assembly defects to primordial dwarfism in humans.