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

Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):12879-84. doi: 10.1073/pnas.0805944105. Epub 2008 Aug 26.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / metabolism*
  • Animals
  • Caenorhabditis elegans / cytology*
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Cycle Proteins / metabolism*
  • Cell Cycle*
  • Chromatin / pathology
  • DNA Replication*
  • Down-Regulation
  • Embryo, Nonmammalian / cytology
  • Nuclear Proteins / metabolism*
  • S Phase
  • Valosin Containing Protein


  • Caenorhabditis elegans Proteins
  • Cell Cycle Proteins
  • Chromatin
  • Nuclear Proteins
  • Ufd-1 protein, C elegans
  • Adenosine Triphosphatases
  • Valosin Containing Protein