A nucleolar AAA-NTPase is required for parasite division

Elena S. Suvorova, Joshua B. Radke, Li Min Ting, Sumiti Vinayak, Carmelo A. Alvarez, Stella Kratzer, Kami Kim, Boris Striepen, Michael W. White

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Summary: Apicomplexa division involves several distinct phases shared with other eukaryote cell cycles including a gap period (G1) prior to chromosome synthesis, although how progression through the parasite cell cycle is controlled is not understood. Here we describe a cell cycle mutant that reversibly arrests in the G1 phase. The defect in this mutant was mapped by genetic complementation to a gene encoding a novel AAA-ATPase/CDC48 family member called TgNoAP1. TgNoAP1 is tightly regulated and expressed in the nucleolus during the G1/S phases. A tyrosine to a cysteine change upstream of the second AAA+ domain in the temperature sensitive TgNoAP1 allele leads to conditional protein instability, which is responsible for rapid cell cycle arrest and a primary defect in 28S rRNA processing as confirmed by knock-in of the mutation back into the parent genome. The interaction of TgNoAP1 with factors of the snoRNP and R2TP complexes indicates this protein has a role in pre-rRNA processing. This is a novel role for a cdc48-related chaperone protein and indicates that TgNoAP1 may be part of a dynamic mechanism that senses the health of the parasite protein machinery at the initial steps of ribosome biogenesis and conveys that information to the parasite cell cycle checkpoint controls.

Original languageEnglish (US)
Pages (from-to)338-355
Number of pages18
JournalMolecular Microbiology
Volume90
Issue number2
DOIs
StatePublished - Oct 2013

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Nucleoside-Triphosphatase
Parasites
Cell Cycle Checkpoints
Cell Cycle
G1 Phase
Small Nucleolar Ribonucleoproteins
Proteins
Apicomplexa
RNA Precursors
Eukaryota
Ribosomes
S Phase
Cysteine
Tyrosine
Adenosine Triphosphatases
Chromosomes
Alleles
Genome
Mutation
Temperature

ASJC Scopus subject areas

  • Molecular Biology
  • Microbiology

Cite this

Suvorova, E. S., Radke, J. B., Ting, L. M., Vinayak, S., Alvarez, C. A., Kratzer, S., ... White, M. W. (2013). A nucleolar AAA-NTPase is required for parasite division. Molecular Microbiology, 90(2), 338-355. https://doi.org/10.1111/mmi.12367

A nucleolar AAA-NTPase is required for parasite division. / Suvorova, Elena S.; Radke, Joshua B.; Ting, Li Min; Vinayak, Sumiti; Alvarez, Carmelo A.; Kratzer, Stella; Kim, Kami; Striepen, Boris; White, Michael W.

In: Molecular Microbiology, Vol. 90, No. 2, 10.2013, p. 338-355.

Research output: Contribution to journalArticle

Suvorova, ES, Radke, JB, Ting, LM, Vinayak, S, Alvarez, CA, Kratzer, S, Kim, K, Striepen, B & White, MW 2013, 'A nucleolar AAA-NTPase is required for parasite division', Molecular Microbiology, vol. 90, no. 2, pp. 338-355. https://doi.org/10.1111/mmi.12367
Suvorova ES, Radke JB, Ting LM, Vinayak S, Alvarez CA, Kratzer S et al. A nucleolar AAA-NTPase is required for parasite division. Molecular Microbiology. 2013 Oct;90(2):338-355. https://doi.org/10.1111/mmi.12367
Suvorova, Elena S. ; Radke, Joshua B. ; Ting, Li Min ; Vinayak, Sumiti ; Alvarez, Carmelo A. ; Kratzer, Stella ; Kim, Kami ; Striepen, Boris ; White, Michael W. / A nucleolar AAA-NTPase is required for parasite division. In: Molecular Microbiology. 2013 ; Vol. 90, No. 2. pp. 338-355.
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