Topic Overview:

DNA replication is a highly controlled cellular process that requires the regulated assembly of multiple protein components to initiate. Precise duplication of the genome is a fundamental process in maintaining cellular integrity in all organisms, and the enzymes responsible are conserved from archaea to humans. Missteps in this process can lead to genomic instabilities and uncontrolled replication as precursors to cancer cell transformations.

Central to both the initiation and elongation stages of DNA replication is the minichromosome maintenance (MCM) helicase. The loading and function of the MCM family of proteins to unwind DNA is one of the most highly controlled events within the cell cycle. Loading proceeds through defined protein complex assembly steps that direct the toroidal hexameric complex around DNA. After unwinding, replication elongation begins with the synthesis of RNA primers by DNA primases before elongation into DNA by DNA polymerases.

Trakselis will discuss recent discoveries of the molecular mechanisms responsible for DNA unwinding by hexameric helicases that have revealed a novel unwinding model. He will also discuss the evolutionary implications of functional primase-helicase complexes. Finally, he will describe work demonstrating that alternative splicing of specialized MCM proteins in humans is surprisingly common, producing different protein isoforms that function in double-strand break repair.