RRC ID 3760
Author Mouysset J, Deichsel A, Moser S, Hoege C, Hyman AA, Gartner A, Hoppe T.
Title Cell cycle progression requires the CDC-48UFD-1/NPL-4 complex for efficient DNA replication.
Journal Proc. Natl. Acad. Sci. U.S.A.
Abstract 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(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(UFD-1/NPL-4) in DNA replication, which is important for cell cycle progression and genome stability.
Volume 105(35)
Pages 12879-84
Published 2008-9-2
DOI 10.1073/pnas.0805944105
PII 0805944105
PMID 18728180
PMC PMC2529102
MeSH Adenosine Triphosphatases / metabolism* Animals Caenorhabditis elegans / cytology* Caenorhabditis elegans / embryology Caenorhabditis elegans Proteins / metabolism* Cell Cycle* Cell Cycle Proteins / metabolism* Chromatin / pathology DNA Replication* Down-Regulation Embryo, Nonmammalian / cytology Nuclear Proteins / metabolism* S Phase Valosin Containing Protein
IF 9.58
Times Cited 42
C.elegans cDNA?