More Information: Minus iconIcon indicating subtraction, or that the element can be closed. Plus IconIcon indicating addition, or that the element can be opened. Arrow (down) icon.An arrow icon, usually indicating that the containing element can be opened and closed.

The Kenneth Marians Lab: Projects

Mechanisms of Replication Fork Reactivation

Orderly progression of the replication fork is essential for the timely and accurate duplication of our genetic material. Although the bacterial replisome is highly processive, capable of synthesizing megabase-long stretches of nascent duplex DNA without dissociating from the template, it is subject to many obstacles that can arrest replication forks. These obstacles can be chemical damage to the template bases (such as the formation of bulky adducts, abasic sites, or intra-strand thymidine dimers as a result of UV irradiation), nicks in one of the template strands, or frank double-strand breaks in the template. It is also the case that frozen protein-DNA complexes and trains of slow-moving RNA polymerases can block replication fork progression.

Chromosome Dynamics, Chromosome Segregation, and Cytokinesis

Our interests in the mechanisms of chromosome segregation arose from our studies on the roles during DNA replication of the four E. coli DNA topoisomerases. In previous studies we have shown that the subunits of topoisomerase IV, the topoisomerase that decatenates the replicated sister chromosomes, are found in different places in the cell: ParC is found at the cell center associated with a number of replisome proteins and ParE is distributed throughout the cell. Furthermore, Topo IV activity manifests only late in the cell cycle, when DNA replication is nearly complete and is focused at the cell center. For the past few years we have been interested in the following questions: Why and how is Topo IV activity regulated? What is the meaning of the physical separation in the cell of the subunits of Topo IV? And, is there an alternative pathway of chromosome decatenation in the cell?