Emerging links between the biological clock and the DNA damage response.
For life forms to survive, they must adapt to their environmental conditions. One such factor that impacts on both prokaryotic and eukaryotic organisms is the light-dark cycle, a consequence of planetary rotation in relation to our sun. In mammals, the daily light cycle has affected the regulation of many cellular processes such as sleep-wake and calorific intake activities, hormone secretion, blood pressure and immune system responses. Such rhythmic behaviour is the consequence of circadian rhythm/biological clock (BC) systems which are controlled in a light stimulus-dependent manner by a master clock called the suprachiasmatic nucleus (SCN) situated within the anterior hypothalamus. Peripheral clocks located in other organs such as the liver and kidneys relay signals from the SCN, which ultimately leads to tightly controlled expression of several protein families that in turn act on a broad range of cellular functions. Work in lower organisms has demonstrated a link between aging processes and BC factors, and studies in both animal models and clinical trials have postulated a role for certain BC-associated proteins in tumourigenesis and cancer progression. Recent exciting data reported within the last year or so have now established a molecular link between specific BC proteins and factors that control the mammalian cell cycle and DNA damage checkpoints. This mini review will focus on these discoveries and emphasise how such BC proteins may be involved, through their interplay with cell cycle/DNA damage response pathways, in the development of human disease such as cancer.
Collis
Spencer J
SJ
DNA Damage Response Lab, Clare Hall Laboratories, Cancer Research UK, Blanch Lane, South Mimms, EN6 3LD, UK.
Boulton
Simon J
SJ
D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D002453:Cell Cycle; D000071877:Checkpoint Kinase 1; D002940:Circadian Rhythm / Q000502:physiology*; D004249:DNA Damage; D004260:DNA Repair; D018816:Genes, cdc; D006801:Humans; D008027:Light; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D013493:Suprachiasmatic Nucleus / Q000502:physiology
D011494:Protein Kinases; C066780:Clk dual-specificity kinases; D011505:Protein-Tyrosine Kinases; D000071877:Checkpoint Kinase 1; D017346:Protein Serine-Threonine Kinases