title: A nucleolar AAA-NTPase is required for parasite division.
abstract: 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.
authors: Departments of Molecular Medicine & Global Health, University of South Florida, Tampa, FL, 33612, USA.
authors: Elena S
authors: ES
authors: Suvorova
authors: Joshua B
authors: JB
authors: Radke
authors: Li-Min
authors: LM
authors: Ting
authors: Sumiti
authors: S
authors: Vinayak
authors: Carmelo A
authors: CA
authors: Alvarez
authors: Stella
authors: S
authors: Kratzer
authors: Kami
authors: K
authors: Kim
authors: Boris
authors: B
authors: Striepen
authors: Michael W
authors: MW
authors: White
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism; D019943:Amino Acid Substitution; D018797:Cell Cycle Proteins / Q000235:genetics; D002455:Cell Division; D002466:Cell Nucleolus / Q000201:enzymology* / Q000648:ultrastructure; D003545:Cysteine / Q000235:genetics; D019143:Evolution, Molecular; D059585:G1 Phase Cell Cycle Checkpoints; D005786:Gene Expression Regulation; D005816:Genetic Complementation Test; D006358:Hot Temperature; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010802:Phylogeny; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012339:RNA, Ribosomal, 28S / Q000235:genetics; D012270:Ribosomes / Q000378:metabolism; D014122:Toxoplasma / Q000166:cytology* / Q000201:enzymology* / Q000235:genetics; D014443:Tyrosine / Q000235:genetics; D000074405:Valosin Containing Protein
chemical_list: D018797:Cell Cycle Proteins; D015800:Protozoan Proteins; D012339:RNA, Ribosomal, 28S; D014443:Tyrosine; D000251:Adenosine Triphosphatases; D000074405:Valosin Containing Protein; D003545:Cysteine
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