MULTIPLE PROTEIN-BINDING SITES IN THE TAS-REGION OF HUMAN AND RAT MITOCHONDRIAL-DNA

To study the molecular mechanisms responsible for the regulation of mi tochondrial DNA copy number, in vivo and in organello dimethyl sulfate footprinting experiments in human fibroblasts and rat liver mitochond ria were carried out. By this approach we identified in both species t wo specific protein binding sites in the 3' region of the displacement loop of mitochondrial DNA. One site contains the TAS-D element of hum an and rat mitochondrial DNA; the other covers TAS-C and TAS-B in huma n, whereas in rat it comprises part of TAS-B. We suggest that the prot ected sequences might be the site of action of protein factors involve d in the premature termination of mitochondrial DNA heavy-strand synth esis. (C) 1998 Academic Press.