The KRAB Zinc Finger Protein Roma/Zfp157 Is a Critical Regulator of Cell-Cycle Progression and Genomic Stability

Teresa L F Ho, Guillaume Guilbaud, J. Julian Blow, Julian E. Sale, Christine J. Watson (Lead / Corresponding author)

    Research output: Contribution to journalArticle

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    Abstract

    Regulation of DNA replication and cell division is essential for tissue growth and maintenance of genomic integrity and is particularly important in tissues that undergo continuous regeneration such as mammary glands. We have previously shown that disruption of the KRAB-domain zinc finger protein Roma/Zfp157 results in hyperproliferation of mammary epithelial cells (MECs) during pregnancy. Here, we delineate the mechanism by which Roma engenders this phenotype. Ablation of Roma in MECs leads to unscheduled proliferation, replication stress, DNA damage, and genomic instability. Furthermore, mouse embryonic fibroblasts (MEFs) depleted for Roma exhibit downregulation of p21Cip1 and geminin and have accelerated replication fork velocities, which is accompanied by a high rate of mitotic errors and polyploidy. In contrast, overexpression of Roma in MECs halts cell-cycle progression, whereas siRNA-mediated p21Cip1 knockdown ameliorates, in part, this phenotype. Thus, Roma is an essential regulator of the cell cycle and is required to maintain genomic stability.

    Original languageEnglish
    Pages (from-to)724-734
    Number of pages11
    JournalCell Reports
    Volume15
    Issue number4
    Early online date14 Apr 2016
    DOIs
    Publication statusPublished - 26 Apr 2016

    Fingerprint

    Genomic Instability
    Zinc Fingers
    Zinc
    Cell Cycle
    Breast
    Epithelial Cells
    Cells
    Geminin
    Tissue
    Phenotype
    Proteins
    Polyploidy
    DNA
    Fibroblasts
    Human Mammary Glands
    Ablation
    DNA Replication
    Cell Division
    Small Interfering RNA
    DNA Damage

    Cite this

    Ho, Teresa L F ; Guilbaud, Guillaume ; Blow, J. Julian ; Sale, Julian E. ; Watson, Christine J. / The KRAB Zinc Finger Protein Roma/Zfp157 Is a Critical Regulator of Cell-Cycle Progression and Genomic Stability. In: Cell Reports. 2016 ; Vol. 15, No. 4. pp. 724-734.
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    abstract = "Regulation of DNA replication and cell division is essential for tissue growth and maintenance of genomic integrity and is particularly important in tissues that undergo continuous regeneration such as mammary glands. We have previously shown that disruption of the KRAB-domain zinc finger protein Roma/Zfp157 results in hyperproliferation of mammary epithelial cells (MECs) during pregnancy. Here, we delineate the mechanism by which Roma engenders this phenotype. Ablation of Roma in MECs leads to unscheduled proliferation, replication stress, DNA damage, and genomic instability. Furthermore, mouse embryonic fibroblasts (MEFs) depleted for Roma exhibit downregulation of p21Cip1 and geminin and have accelerated replication fork velocities, which is accompanied by a high rate of mitotic errors and polyploidy. In contrast, overexpression of Roma in MECs halts cell-cycle progression, whereas siRNA-mediated p21Cip1 knockdown ameliorates, in part, this phenotype. Thus, Roma is an essential regulator of the cell cycle and is required to maintain genomic stability.",
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    The KRAB Zinc Finger Protein Roma/Zfp157 Is a Critical Regulator of Cell-Cycle Progression and Genomic Stability. / Ho, Teresa L F; Guilbaud, Guillaume; Blow, J. Julian; Sale, Julian E.; Watson, Christine J. (Lead / Corresponding author).

    In: Cell Reports, Vol. 15, No. 4, 26.04.2016, p. 724-734.

    Research output: Contribution to journalArticle

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