Human mitochondrial topoisomerase I

Tension generated in the circular mitochondrial genome during replication a nd transcription points to the need for mtDNA topoisomerase activity. Here we report a 601-aa polypeptide highly homologous to nuclear topoisomerase 1 . The N-terminal domain of this novel topoisomerase contains a mitochondria l localization sequence and lacks a nuclear localization signal. Therefore, we refer to this polypeptide as top1mt. The pattern of top1mt expression m atches the requirement for high mitochondrial activity in specific tissues. top1mt is a type IB topoisomerase that requires diva lent metal (Ca2+ or M g2+) and alkaline pH for optimum activity. The TOP1mt gene is highly homolo gous to the nuclear TOP1 gene and consists of 14 exons. IL IS localized on human chromosome 8q24.3.