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Coupling of human circadian and cell cycles by the timeless protein

Keziban Unsal-Kaçmaz1, Thomas E Mullen, William K Kaufmann

  • 1Department of Biochemistry and Biophysics, Mary Ellen Jones Building CB 7260, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.

Molecular and Cellular Biology
|March 31, 2005
PubMed

Insights

The Timeless protein is crucial for circadian rhythms and DNA damage response in humans. Its interaction with key proteins highlights a link between cell cycle checkpoints and the body's internal clock.

Area of Science:

  • Molecular Biology
  • Chronobiology
  • Cell Biology

Background:

  • The Timeless protein is vital for circadian rhythms in Drosophila and mice.
  • Its mammalian orthologue is essential for viability and maintaining circadian rhythm robustness.

Purpose of the Study:

  • To investigate the role of human Timeless protein in cellular processes.
  • To explore the interaction of Timeless with circadian and DNA damage response proteins.

Main Methods:

  • Investigated protein interactions using co-immunoprecipitation.
  • Assessed DNA damage checkpoint function via cell-based assays.
  • Analyzed the impact of Timeless down-regulation on replication and intra-S checkpoints.

Main Results:

  • Human Timeless protein interacts with cryptochrome 2 (circadian clock) and Chk1/ATR-ATRIP (DNA damage checkpoints).
  • Timeless plays a significant role in the DNA damage checkpoint response.
  • Down-regulation of Timeless impairs replication and intra-S checkpoints in human cells.

Conclusions:

  • The Timeless protein mediates an essential connection between the circadian cycle and DNA damage checkpoints.
  • This finding reveals a novel regulatory role for Timeless in maintaining genomic stability and circadian function.

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