DR. CAROLINE SCHILD-POULTER
DNA Repair: Mending Broken Genes
Repair jobs are such nuisances! They pop up at the most inconvenient times and in annoying groups, rather than as single, tolerable entities. Even quick, five-minute repairs often turn into five-hour ordeals. However, some people have a knack for fixing that leaky faucet, squeaky door, or drafty window. If you lack those invaluable ‘fixit’ genes, you can hire genetically blessed people who can build, fix, and replace almost anything. Cells have also developed a repair system for fixing broken parts. Dr. Caroline Schild-Poulter at the Robarts Research Institute and in the Dept. of Biochemistry at Western University studies the cellular system for DNA repair.
DNA repair is critical for ensuring DNA stability and suppressing cancer. Our genetic material is constantly at risk for DNA damage caused by intracellular and extracellular agents. Reactive intracellular molecules, ionizing radiation, and environmental chemicals harm our genes. DNA double-strand breaks (DSBs) are one form of DNA damage that changes chromosome structure, often resulting in cell death or cancer. An intricate repair system exists for mending DSBs. These repair tools consist of signaling pathways in which protein complexes act in series to fix the damaged DNA. In the first step of this process, the presence of DSBs triggers this pathway. Next, cells stop dividing and repair molecules are activated so that the DNA damage can be fixed. Then, if too much DNA damage is present, cells undergo programmed cell death (apoptosis) to remove the faulty DNA.
Dr. Schild-Poulter explores the cellular response to DNA damage. In particular, she examines the signaling pathways for DNA repair that are activated by DSBs. Her research spans two projects. In the first one, she analyzes domains in Ku70/Ku 80 that contribute to DSB repair. The Ku70/Ku80 dimer binds to DSB ends and recruits DNA-dependent protein kinase catalytic subunit (DNA-PKcs). The resulting trimer becomes activated to carry out downstream effects in the repair pathway. This research will reveal how Ku functions in signaling pathways activated by DNA damage. In her second project, Dr. Schild-Poulter studies the role of Ran-binding protein M (RanBPM) in apoptosis triggered by DNA damage. Such work examines the molecular mechanisms by which RanBPM regulates signaling molecules involved in apoptosis.
To investigate DSB repair pathways, Dr. Schild-Poulter uses molecular biology, cell culture lines, and biochemical assays. Mutations in Ku or RanBPM are expressed in recombinant proteins that are tested for downstream effects on partner binding, apoptosis, and DNA repair pathways. In addition, yeast 2-hybrid screens allow analysis of protein-protein interactions. Dr. Schild-Poulter’s research will contribute to our understanding of the tools used by cells to mend broken genes and the integral role of these tools in cancer prevention. DNA repair, like all repair jobs, is a necessity of life.
This research is funded by the Canadian Institutes of Health Research (CIHR), Natural Sciences and Engineering Research Council of Canada (NSERC), Canada Foundation for Innovation (CFI), and Western University.
© Lynn Weir, 2009
Profile for Dr. Caroline Schild-Poulter
Dr. Caroline Schild-Poulter
Assistant Professor – Dept. of Biochemistry
Scientist – Robarts Research Institute
3rd floor Robarts
P.O. Box 5015, 100 Perth Drive
London, ON N6A 5K8
519-663-5777, ext. 24164
- BSc, MSc, PhD (University of Lausanne, Lausanne, Switzerland)
- Post-doctoral researcher (Institut de Biologie Moléculaire et Cellulaire du CNRS, Strasbourg, France; Loeb Health Research Institute, Ottawa, ON, Canada)
- DNA damage
- DNA repair
- Ku/DNA-PK (DNA-dependent protein kinase)
- RanBPM (Ran-binding protein M)
- stress response
- ionizing radiation
- environmental stresses
Updated by L.Weir, June 2012