Posted on Jan 13, 2012, 6 a.m.
Discovery in DNA repair mechanism may lead to innovative approaches to diagnose and treat cancers.
Occurring when the body is exposed to excessive amounts of electrically charged, aggressive oxygen compounds, oxidative stress is a condition that is linked to an increased risk of various diseases including cancer, Alzheimer's, and cardiovascular disease. In the case of ongoing stress, exposure to UV light or X-rays, the oxidative stress may overwhelm the body's natural defenses, with the aggressive oxygen compounds damaging genetic material, resulting in harmful 8-oxo-guanine base mutations in the DNA. Enni Markkanen, from the University of Zurich-Irchel (Switzerland), and colleagues have decoded and characterized the repair mechanism for the mutated DNA bases. This mechanism efficiently copies thousands of 8-oxo-guanines without their harmful mutations, thus normally preventing the negative consequences of 8-oxo-guanine damage. Outlining the detailed processes involved in the local and temporal coordination of this repair mechanism, the study authors are hopeful that the “DNA repair mechanism discovered here will lead to less invasive approaches in cancer therapy and that it will be possible to develop new clinical tests for the early detection of certain types of cancer.”
Enni Markkanen, Barbara van Loon, Elena Ferrari, Jason L. Parsons, Grigory L. Dianov, Ulrich Hubscher. “Regulation of oxidative DNA damage repair by DNA polymerase [lamda] and MutYH by cross-talk of phosphorylation and ubiquitination.” PNAS, December 27, 2011.