Emerging links between the biological clock and the DNA damage response |
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Authors: | Spencer J Collis Simon J Boulton |
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Institution: | (1) DNA Damage Response Lab, Clare Hall Laboratories, Cancer Research UK, Blanch Lane, South Mimms, EN6 3LD, UK |
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Abstract: | 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. |
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