GMGM seminar of Wolfram S. KUNZ "Removal of oxidative lesions in mtDNA"

Prof. Dr. Wolfram S. KUNZ from University of Bonn (Germany) will give a seminar on October 27 at 11 am in the Seminar room of IPCB:

In work with the mitochondrially-expressed restriction endonucleases mtEagI and mtPstI, we have identified the components of the mtDNA degradation machinery, which include MGME1, POLGexo and TWNK. The mtDNA degradation machinery is essentially a complex exonuclease with degradation pausing-sites proximal to GC-rich stretches. Under conditions of oxidative stress elicited in form of H2O2 pulses, prominent damage of mtDNA is detectable, while nuclear DNA remains mainly intact. This can be explained by the high iron content of mitochondria, which is required for Fenton-reaction dependent formation of the hydroxyl radical. The occurring mtDNA damage consists of single-strand breaks, but also remarkable levels of double-strand breaks. The latter fact is explained by the presence of vulnerable sites in the D-loop region. mtDNA molecules containing double-strand breaks are rapidly degraded, while single-strand breaks are repaired in the LIG3-dependent base excision repair pathway. Degradation of linear mtDNA is therefore considered as an important quality control mechanism to maintain intactness of the mitochondrial genome and to prevent deletion formation.