Adaptation of topoisomerase I paralogs to nuclear and mitochondrial DNA

Ilaria Dalla Rosa, Steffi Goffart, Melanie Wurm, Constanze Wiek, Frank Essmann, Stefan Sobek, Peter Schroeder, Hongliang Zhang, Jean Krutmann, Helmut Hanenberg, Klaus Schulze-Osthoff, Christian Mielke, Yves Pommier, Fritz Boege, Morten O. Christensen

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Topoisomerase I is essential for DNA metabolism in nuclei and mitochondria. In yeast, a single topoisomerase I gene provides for both organelles. In vertebrates, topoisomerase I is divided into nuclear and mitochondrial paralogs (Top1 and Top1mt). To assess the meaning of this gene duplication, we targeted Top1 to mitochondria or Top1mt to nuclei. Overexpression in the fitting organelle served as control. Targeting of Top1 to mitochondria blocked transcription and depleted mitochondrial DNA. This was also seen with catalytically inactive Top1 mutants, but not with Top1mt overexpressed in mitochondria. Targeting of Top1mt to the nucleus revealed that it was much less able to interact with mitotic chromosomes than Top1 overexpressed in the nucleus. Similar experiments with Top1/Top1mt hybrids assigned these functional differences to structural divergences in the DNA-binding core domains. We propose that adaptation of this domain to different chromatin environments in nuclei and mitochondria has driven evolutional development and conservation of organelle-restricted topoisomerase I paralogs in vertebrates.

Original languageEnglish (US)
Pages (from-to)6414-6428
Number of pages15
JournalNucleic acids research
Volume37
Issue number19
DOIs
StatePublished - 2009
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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    Rosa, I. D., Goffart, S., Wurm, M., Wiek, C., Essmann, F., Sobek, S., Schroeder, P., Zhang, H., Krutmann, J., Hanenberg, H., Schulze-Osthoff, K., Mielke, C., Pommier, Y., Boege, F., & Christensen, M. O. (2009). Adaptation of topoisomerase I paralogs to nuclear and mitochondrial DNA. Nucleic acids research, 37(19), 6414-6428. https://doi.org/10.1093/nar/gkp708