Coordinating Functions at the Replication Fork
Mechanism & Control of Replication Initiation
Activation of DNA Damage Signaling
Mechanisms of Genomic Stability
For more details, go to the ASBMB Meeting 2013 program page
and click to expland “Genome Replication and Repair.”
Genome integrity is central to maintaining cellular and organismal identity and preventing the development of diseases including cancer. Although early studies focused on DNA polymerase fidelity and DNA repair mechanisms, it has become clear that many other events contribute to genome maintenance. For example, the replication fork not only replicates the DNA but also coordinates many other functions required for genome stability.
The speakers in the first session will address how the replication fork facilitates chromatin assembly, detecting DNA damage and eliminating potential roadblocks. The coordination revealed by these studies illustrates how replication forks are the focus of many aspects of chromatin function beyond simple DNA replication.In addition, it has become clear that activation of the eukaryotic replicative helicase is a multistep event involving both DNA and protein remodeling. The second session will explore the mechanisms that drive these events and how higher order structure of the chromatin influences the temporal regulation of origin activation.
In addition, it has become clear that activation of the eukaryotic replicative helicase is a multistep event involving both DNA and protein remodeling. The second session will explore the mechanisms that drive these events and how higher chromatin order structure influences the temporal regulation of origin activation during S phase.
When DNA damage occurs, cells need to respond instantly to prevent structural alterations on DNA from converting into heritable mutations. This response involves complex signaling pathways that extend well beyond the enzymes that remove the DNA damage. The third session will highlight current investigations of DNA damage signaling mechanisms, including initiation and optimization of damage checkpoint signaling, regulation of recombination and threading of the damage-signaling cascade via ubiquitination.
The last session will cover mechanistic aspects of how compromised genome stability leads to cancer. Clearly, a large set of genetic alterations is required to render a cell cancerous. At the chromosomal level, tumor-suppressing mechanisms can be compromized by cumulative and selective deletion of regions encompassing antiproliferation genes, invoking the cancer gene island concept. At the DNA level, endogenous metabolites can be a major source of mutations when pathways countering their actions are defective. These recent advances are mechanistically informative and pertinent to cancer etiology.
Stephen Bell (email@example.com) is a professor at the Massachusetts Institute of Technology and a Howard Hughes Medical Institute investigator. Lei Li (firstname.lastname@example.org) is a professor at the University of Texas MD Anderson Cancer Center.