Melatonin is secreted from the pineal gland at night in both nocturnal and diurnal animals. Once light information reaches the SCN, it signals via a multi-synaptic pathway to the pineal gland to regulate production and secretion of melatonin. Indeed, photo entrainment persists in melanopsin-deficient mice but not in triple knockouts that lack melanopsin, rod, and cone function. The SCN also receives indirect input from ipRGCs via the intergeniculate leaflet and input from rods and cones. In mammals, light information travels directly from intrinsically photosensitive melanopsin-containing retinal ganglion cells (ipRGC) in the eye through the retinohypothalamic tract to the SCN. Light at night: Light is the most potent synchronizing factor for the SCN. For example, RevErb and Per3 were not initially considered critical for maintaining circadian clock function however, the importance of these genes for circadian regulation is now widely accepted. Several secondary and tertiary clock components have been identified as necessary for the generation of precise circadian rhythms, and the criteria for what constitutes core clock genes are continuously evolving. In addition to the primary feedback loop, several additional regulatory loops influence the circadian clockwork, but the core clock components described above are protein products of clock genes that are essential for generation and regulation of circadian rhythms Ablation of any of the core clock genes, Clock or Bmal1, Per1 or Per2, or Cry1 or Cry2, disrupts circadian organization. This process requires about 24 h to complete a full cycle. As the levels of these proteins increase, PER and CRY begin to form a heterodimer complex that translocates back to the nucleus to associate with CLOCK and BMAL1 to repress their own transcription. Period (PER) and cryptochrome (CRY) proteins accumulate in the cytoplasm throughout the day.
The proteins, circadian locomotor output cycles kaput (CLOCK), and brain and muscle arnt-like protein 1 (BMAL1) form heterodimers that promote expression of period ( Per1, Per2, and Per3) and cryptochrome ( Cry1 and Cry2) via E-box enhancers. Our search engines for the manuscript were PubMed and Google Scholar and our primary search terms were ‘light at night and cancer, light at night and circadian disruption, clock genes and cell cycle, and clock genes and cancer’.Īt a molecular level, the mammalian circadian system is driven by an autoregulatory feedback loop of transcriptional activators and repressors. Finally, we provide some strategies for mitigation of disrupted circadian rhythms to improve health. Next, we review the clinical implications of disrupted circadian rhythms on cancer, followed by a section on the foundational science literature on the effects of light at night and cancer. Then, we describe the role of circadian rhythms on the cell cycle, as well as the contribution of clock genes to oncogenesis. Below, we present a brief review of the molecular circadian clock system and the importance of light during the day and darkness at night. As described below, common modern disruptors of circadian rhythms include night shift work, experiencing so-called ‘social jet lag’, which is shifted sleep-wake cycles between weekends and work days, and instances of exposure to light at night.
Disruption of circadian rhythms dramatically influences cell division and cancer development, whereas malignant transformation disrupts circadian organization. There is a bidirectional relationship between circadian rhythms and cell division. For example, cell division shows strong daily cycles. Importantly, several key processes involved in cancer are governed by circadian rhythms.
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