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

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

    Research output: Contribution to journalArticle

    48 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)12879-12884
    Number of pages6
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume105
    Issue number35
    DOIs
    Publication statusPublished - 2 Sep 2008

    Keywords

    • ATL-1/ATR
    • C. elegans
    • CDC-48/p97
    • genome stability
    • UNFOLDED PROTEIN RESPONSE
    • AAA-ATPASE P97/VCP
    • CAENORHABDITIS-ELEGANS
    • MEMBRANE-FUSION
    • C-ELEGANS
    • RECOMBINATION PROTEIN
    • UBIQUITIN
    • MITOSIS
    • P97
    • CDC48/P97

    Cite this

    Mouysset, Julien ; Deichsel, Alexandra ; Moser, Sandra ; Hoege, Carsten ; Hyman, Anthony A. ; Gartner, Anton ; Hoppe, Thorsten. / Cell cycle progression requires the CDC-48(UFD-1/NPL-4) complex for efficient DNA replication. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 35. pp. 12879-12884.
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    Cell cycle progression requires the CDC-48(UFD-1/NPL-4) complex for efficient DNA replication. / Mouysset, Julien; Deichsel, Alexandra; Moser, Sandra; Hoege, Carsten; Hyman, Anthony A.; Gartner, Anton; Hoppe, Thorsten.

    In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 35, 02.09.2008, p. 12879-12884.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Cell cycle progression requires the CDC-48(UFD-1/NPL-4) complex for efficient DNA replication

    AU - Mouysset, Julien

    AU - Deichsel, Alexandra

    AU - Moser, Sandra

    AU - Hoege, Carsten

    AU - Hyman, Anthony A.

    AU - Gartner, Anton

    AU - Hoppe, Thorsten

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    N2 - 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.

    AB - 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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