Differential regulation of the catalytic and accessory subunit genes of Drosophila mitochondrial DNA polymerase

The developmental pattern of expression of the genes encoding the catalytic (alphay) and accessory (beta) subunits of mitochondrial DNA polymerase (po l gamma) has been examined in Drosophila melanogaster. The steady-state lev el of pol gamma-beta mRNA increases during the first hours of development, reaching its maximum value at the start of mtDNA replication in Drosophila embryos. In contrast, the steady-state level of pol gamma-alpha mRNA decrea ses as development proceeds and is low in stages of active mtDNA replicatio n. This difference in mRNA abundance results at least in part from differen ces in the rates of mRNA synthesis. The pol gamma genes are located in a co mpact cluster of five genes that contains three promoter regions (P1-P3), T he P1 region directs divergent transcription of the pol gamma-beta gene and the adjacent rpII33 gene. P1 contains a DNA replication-related element (D RE) that is essential for pol gamma-beta promoter activity, but not for rpI I33 promoter activity in Schneider's cells. A second divergent promoter reg ion (P2) controls the expression of the orc5 and sop2 genes. The P2 region contains two DREs that are essential for orc5 promoter activity, but not fo r sop2 promoter activity. The expression of the pol gamma-alpha gene is dir ected by P3, a weak promoter that does not contain DREs, Electrophoretic mo bility shift experiments demonstrate that the DRE-binding factor (DREF) reg ulatory protein binds to the DREs in P1 and P2, DREF regulates the expressi on of several genes encoding key factors involved in nuclear DNA replicatio n. Its role in controlling the expression of the pol gamma-beta and orc5 ge nes establishes a common regulatory mechanism linking nuclear and mitochond rial DNA replication. Overall, our results suggest that the accessory subun it of mtDNA polymerase plays an important role in the control of mtDNA repl ication in Drosophila.