Circadian proteins in the regulation of cell cycle and genotoxic stress responses

Trends Cell Biol. 2007 Jul;17(7):311-7. doi: 10.1016/j.tcb.2007.07.001. Epub 2007 Jul 20.


The mammalian circadian system has been implicated in the regulation of the genotoxic stress response of an organism; however, the underlying molecular mechanisms are not well understood. Recent data suggest that, in addition to circadian variations in the expression of genes involved in genotoxic stress responses, core circadian proteins PERIOD1 (PER1) and TIMELESS (TIM) interact with components of the cell cycle checkpoint system, such as ataxia telangiectasia mutated (ATM)-checkpoint kinase 2 (Chk2) and ataxia telangiectasia and Rad3-related (ATR)-Chk1, and are necessary for activation of Chk1 and Chk2 by DNA damage. Moreover, in complex with its recently identified partner, TIM-interacting protein (TIPIN), TIM interacts with components of the DNA replication system to regulate DNA replication processes under both normal and stress conditions. These discoveries shed new light on the role of core circadian proteins in various cellular and physiological processes.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cell Cycle Proteins / metabolism
  • Cell Cycle*
  • Checkpoint Kinase 2
  • Circadian Rhythm*
  • DNA Damage
  • Drosophila
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Models, Biological
  • Mutagens
  • Oscillometry
  • Period Circadian Proteins
  • Protein Serine-Threonine Kinases / metabolism


  • Cell Cycle Proteins
  • Intracellular Signaling Peptides and Proteins
  • Mutagens
  • PER1 protein, human
  • Period Circadian Proteins
  • TIMELESS protein, human
  • Checkpoint Kinase 2
  • CHEK2 protein, human
  • Protein Serine-Threonine Kinases