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Related Experiment Videos

Tumor suppression and circadian function.

Misty Chen-Goodspeed1, Cheng Chi Lee

  • 1Department of Biochemistry and Molecular Biology, University of Texas Health Science Center, Houston, TX 77030, USA.

Journal of Biological Rhythms
|July 31, 2007
PubMed
Summary
This summary is machine-generated.

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The circadian clock regulates cell division and DNA repair. Genes PER1 and PER2, involved in circadian rhythms, act as tumor suppressors by aiding DNA damage response pathways.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • The circadian clock (body's time-keeping system) and cell division cycle (regulating development and renewal) are fundamental biological processes.
  • Cell cycle gene expression (e.g., Wee1, Cyclins, c-Myc) is controlled by the circadian transcriptional complex (CLOCK/NPAS2 with BMAL1).
  • The repressors CRY1 and CRY2 periodically inhibit gene expression of circadian regulators PER1, PER2, CRY1, and CRY2.

Purpose of the Study:

  • To investigate the role of circadian rhythm regulators PER1 and PER2 in DNA damage response pathways.
  • To explore the link between circadian function and tumor suppression.

Main Methods:

  • Examined gene dosage effects of PER1 and PER2 in cancer cells.
  • Conducted in vivo studies using mice deficient in mPer2.

Related Experiment Videos

  • Investigated the involvement of PER1 and PER2 in ATM-Chk1/Chk2 DNA damage response pathways.

    • Main Results:

    • Overexpression of PER1 or PER2 inhibited neoplastic growth and increased apoptosis in cancer cells.
    • Mice deficient in mPer2 exhibited higher tumor incidence after genotoxic stress.
    • PER1 and PER2 are implicated in ATM-Chk1/Chk2 DNA damage response pathways.

    Conclusions:

    • PER1 and PER2 play a role in DNA damage response pathways.
    • Normal circadian function, mediated by PER1 and PER2, contributes to tumor suppression.
    • Loss and dysregulation of PER1 and PER2 are observed in human cancers.