Mitochondrial tyrosyl-DNA phosphodiesterase 2 and its TDP2^S short isoform.

ABSTRACT: Tyrosyl-DNA phosphodiesterase 2 (TDP2) repairs abortive topoisomerase II cleavage complexes. Here, we identify a novel short isoform of TDP2 (TDP2^S) expressed from an alternative transcription start site. TDP2^S contains a mitochondrial targeting sequence, contributing to its enrichment in the mitochondria and cytosol, while full-length TDP2 contains a nuclear localization signal and the ubiquitin-associated domain in the N-terminus. Our study reveals that both TDP2 isoforms are present and active in the mitochondria. Comparison of isogenic wild-type (WT) and TDP2 knockout (TDP2^-/-/-) DT40 cells shows that TDP2^-/-/- cells are hypersensitive to mitochondrial-targeted doxorubicin (mtDox), and that complementing TDP2

SUBMITTER: Huang SN 

PROVIDER: S-EPMC5836098 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature