Expression of DNA repair and apoptosis genes in mitochondrial mutant and normal cells following exposure to ionizing radiation

✍ Scribed by Rohan Kulkarni; Robert A. Thomas; James D. Tucker

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 731 KB
• Volume: 52
• Category: Article
• ISSN: 0893-6692
• DOI: 10.1002/em.20605

✦ Synopsis

Abstract

In double‐strand DNA damage repair, nonhomologous end joining (NHEJ) is more error‐prone than homologous recombination repair (HRR), indicating that the relative prevalence of NHEJ may lead to more incorrect repair and thus to increases in chromosome damage. If DNA damage is extensive and cells are unable to repair that damage they typically undergo apoptosis. The mechanism(s) by which cells decide to switch from DNA repair to apoptosis is unknown. Since DNA repair and apoptosis are both energy‐demanding processes, the answer may involve ATP utilization. We used human mitochondrial mutant cell lines obtained from people with phenotypic manifestations of compromised ATP generation. We hypothesized that these cells may not have adequate capacity for dealing with the additional demands for ATP required for repairing DNA damage after genotoxic exposure, perhaps making the cells more prone to undergo apoptosis instead of initiating repair. This study describes changes in the expression of genes involved in NHEJ or HRR, as well as genes involved in apoptosis, in one normal and two mitochondrial mutant human cell lines following ionizing radiation exposure. Compared to normal cells, both mutant cell lines showed reduced expression of genes involved in NHEJ and HRR. Analysis of expression changes in genes involved in apoptosis revealed marked increases in expression in the mutants compared to normal cells. These results indicate that following ionizing radiation exposure, mitochondrial mutant cells have decreased levels of mRNA expression of DNA repair genes and increased expression levels of genes involved in apoptosis compared to normal cells. This study provides information that might be useful in characterizing energy dependent processes following exposure to stress or genotoxic agents. Environ. Mol. Mutagen., 2011. © 2010 Wiley‐Liss, Inc.