Monday, August 26, 2013

A nucleolar AAA-NTPase is required for parasite division

2013 Aug 22. doi: 10.1111/mmi.12367. [Epub ahead of print]

A nucleolar AAA-NTPase is required for parasite division


Departments of Molecular Medicine & Global Health, University of South Florida, Tampa, FL 33612.


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.
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AAA-ATPase, Apicomplexa, G1 phase, Toxoplasma gondii, cell cycle, nucleolus, replication
[PubMed - as supplied by publisher]

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