Replication initiation mechanisms
In all cells, the onset of DNA replication is controlled by dedicated ATPases that assist with origin recognition, helicase loading, and at times the melting of parental template DNA strands. How these ‘initiator’ 
factors coordinately assemble with appropriate nucleic acid substrates and each other to promote replisome assembly is not understood at a molecular level. We determined that all cellular replication initiators are predicated on a common AAA+ ATPase fold, but that bacterial, archaeal and eukaryotic initiator homologs assemble into markedly different oligomeric complexes that interact with client DNA substrates in highly distinct manners. Our work has helped resolve both recent and long-standing problems, from how certain mutations implicated in primordial dwarfism disorders impact the assembly of the eukaryotic Origin Recognition Complex (ORC) to how bacterial DnaA recognizes and melts replication origins.