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Murine dihydrofolate reductase transcripts through the cell cycle.

P J Farnham, R T Schimke

    Molecular and Cellular Biology
    |February 1, 1986
    PubMed
    Summary
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    Cell-cycle regulation of dihydrofolate reductase (DHFR) involves transcriptional control. DHFR gene expression increases at the G1/S phase boundary without altering transcription initiation or polyadenylation sites.

    Area of Science:

    • Molecular Biology
    • Gene Regulation
    • Cell Cycle Biology

    Background:

    • The dihydrofolate reductase (DHFR) gene exhibits complex transcript variants.
    • DHFR promoter activity is bidirectional, producing multiple RNA species.
    • Understanding DHFR gene regulation during the cell cycle is crucial.

    Purpose of the Study:

    • To investigate the cell-cycle-dependent production of DHFR transcripts.
    • To analyze the heterogeneity of DHFR RNA termini throughout the cell cycle.
    • To elucidate the mechanism of DHFR transcriptional regulation.

    Main Methods:

    • Analysis of DHFR RNA production in mouse 3T6 cells.
    • Monitoring RNA termini and transcript levels during cell cycle progression.
    • Quantification of different DHFR transcript variants.

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    Main Results:

    • All DHFR transcripts showed similar cell-cycle traversal patterns.
    • Transcript levels increased at the G1/S phase boundary.
    • Relative ratios of different transcripts remained constant throughout the cell cycle.

    Conclusions:

    • Cell-cycle regulation of DHFR is achieved by modulating transcription efficiency, not initiation sites.
    • Polyadenylation site usage remains constant during the cell cycle.
    • Transcriptional regulation of DHFR involves transient increases in promoter activity.