Trypanosomes Have Six Mitochondrial DNA Helicases with One Controlling Kinetoplast Maxicircle Replication

Beiyu Liu, Jianyang Wang, Nurit Yaffe, Megan E. Lindsay, Zhixing Zhao, Aviad Zick, Joseph Shlomai, Paul T. Englund

Research output: Contribution to journalArticle

Abstract

Kinetoplast DNA (kDNA), the trypanosome mitochondrial DNA, contains thousands of minicircles and dozens of maxicircles interlocked in a giant network. Remarkably, Trypanosoma brucei's genome encodes 8 PIF1-like helicases, 6 of which are mitochondrial. We now show that TbPIF2 is essential for maxicircle replication. Maxicircle abundance is controlled by TbPIF2 level, as RNAi of this helicase caused maxicircle loss, and its overexpression caused a 3- to 6-fold increase in maxicircle abundance. This regulation of maxicircle level is mediated by the TbHslVU protease. Previous experiments demonstrated that RNAi knockdown of TbHslVU dramatically increased abundance of minicircles and maxicircles, presumably because a positive regulator of their synthesis escaped proteolysis and allowed synthesis to continue. Here, we found that TbPIF2 level increases following RNAi of the protease. Therefore, this helicase is a TbHslVU substrate and an example of a positive regulator, thus providing a molecular mechanism for controlling maxicircle replication.

Original languageEnglish (US)
Pages (from-to)490-501
Number of pages12
JournalMolecular cell
Volume35
Issue number4
DOIs
StatePublished - Aug 28 2009

Keywords

  • DNA
  • MICROBIO
  • PROTEINS

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Trypanosomes Have Six Mitochondrial DNA Helicases with One Controlling Kinetoplast Maxicircle Replication'. Together they form a unique fingerprint.

  • Cite this

    Liu, B., Wang, J., Yaffe, N., Lindsay, M. E., Zhao, Z., Zick, A., Shlomai, J., & Englund, P. T. (2009). Trypanosomes Have Six Mitochondrial DNA Helicases with One Controlling Kinetoplast Maxicircle Replication. Molecular cell, 35(4), 490-501. https://doi.org/10.1016/j.molcel.2009.07.004