Prof. Michael Trakselis, University of Pittsburgh

Protein Complex Assemblies and Activities at the Replication Fork

Biochemistry Division Seminar Series

The DNA replication machinery in archaea contains all the core components found in higher eukaryotes, yet provides a simple model system to examine the functionalities, dynamics, and interactions involved in this essential metabolic process. I will discuss our recent progress in dissecting the molecular interactions required for large protein complex assemblies and their resulting enzymatic abilities. Specifically, we have revealed a novel model of MCM helicase unwinding termed the Steric Exclusion and Wrapping (SEW), where both separated strands of DNA participate in the mechanism. Initiation of DNA synthesis requires the action of a DNA primase, and in archaea and unlike all other organisms, we have discovered two separate and active classes of DNA primases. Handoff of the thermodynamically unstable RNA primer occurs through the concerted action of the clamp and clamp loader to form the active DNA polymerase holoenzyme complex. Complicating this assembly process is our discovery that multiple DNA polymerases can interact to form a variety of higher order states that increase the DNA synthesis and lesion bypass abilities. In all, DNA replication enzymes from archaea have provided insights into conserved molecular processes found in higher eukaryotes but also have unique features that may aid growth at high temperatures.

For more information contact Prof. Raquel Lieberman (404-385-3663).