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

Mouysset Julien | Zendy; Alexandra Deichsel | Zendy; Sandra Moser | Zendy; Carsten Hoege | Zendy; Anthony A. Hyman | Zendy; Anton Gartner | Zendy; Thorsten Hoppe | Zendy

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

Author(s) -

Mouysset Julien,

Alexandra Deichsel,

Sandra Moser,

Carsten Hoege,

Anthony A. Hyman,

Anton Gartner,

Thorsten Hoppe

Publication year - 2008

Publication title -

proceedings of the national academy of sciences

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 5.011

H-Index - 771

eISSN - 1091-6490

pISSN - 0027-8424

DOI - 10.1073/pnas.0805944105

Subject(s) - control of chromosome duplication , dna replication , licensing factor , origin recognition complex , cell cycle , pre replication complex , dna replication factor cdt1 , replication factor c , microbiology and biotechnology , biology , eukaryotic dna replication , cell division , dna re replication , mitosis , dna synthesis , s phase , caenorhabditis elegans , genetics , dna , cell , gene

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.

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