Cell cycle progression requires the CDC-48 super(UFD-1/NPL-4) complex for efficient DNA replication

Since cdc48 mutants were isolated by the first genetic screens for cell division cycle (cdc) mutants in yeast, the requirement of the chaperone-like ATPase Cdc48/p97 during cell division has remained unclear. Here, we discover an unanticipated function for Caenorhabditis elegans CDC-48 in DNA replic...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2008-09, Vol.105 (35), p.12879-12884
Main Authors: Mouysset, Julien, Deichsel, Alexandra, Moser, Sandra, Hoege, Carsten, Hyman, Anthony A, Gartner, Anton, Hoppe, Thorsten
Format: Article
Language:English
Subjects:
Adenosinetriphosphatase
Caenorhabditis elegans
Cell cycle
Cell division
DNA biosynthesis
Embryogenesis
Genetic screening
Genomes
Hypersensitivity
Replication
S phase
Stress
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Summary:Since cdc48 mutants were isolated by the first genetic screens for cell division cycle (cdc) mutants in yeast, the requirement of the chaperone-like ATPase Cdc48/p97 during cell division has remained unclear. Here, we discover an unanticipated function for Caenorhabditis elegans CDC-48 in DNA replication linked to cell cycle control. Our analysis of the CDC-48 super(UFD-1/NPL-4) complex identified a general role in S phase progression of mitotic cells essential for embryonic cell division and germline development of adult worms. These developmental defects result from activation of the DNA replication checkpoint caused by replication stress. Similar to loss of replication licensing factors, DNA content is strongly reduced in worms depleted for CDC-48, UFD-1, and NPL-4. In addition, these worms show decreased DNA synthesis and hypersensitivity toward replication blocking agents. Our findings identified a role for CDC-48 super(UFD-1/NPL-4) in DNA replication, which is important for cell cycle progression and genome stability.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0805944105