Circadian rhythm of cell division

Smaaland, Rune

doi:10.1007/978-1-4615-5873-6_23

Cited by 41 publications

(21 citation statements)

References 110 publications

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“…The mammalian epidermis is now emerging as a prime model to study the role of the circadian clock in cell proliferation and cancer susceptibility (8,12,13). Previous studies have established circadian variation in proliferation in several tissues, including mouse epidermis (21). Our study extends these results by showing time-of-day-dependent variation in proliferation in the upper follicle as well as in the secondary hair germ and matrix of growing hair follicles.…”

Section: Discussionsupporting

confidence: 77%

Brain and muscle Arnt-like protein-1 (BMAL1) controls circadian cell proliferation and susceptibility to UVB-induced DNA damage in the epidermis

Geyfman¹,

Kumar

Liu³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

223

322

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The role of the circadian clock in skin and the identity of genes participating in its chronobiology remain largely unknown, leading us to define the circadian transcriptome of mouse skin at two different stages of the hair cycle, telogen and anagen. The circadian transcriptomes of telogen and anagen skin are largely distinct, with the former dominated by genes involved in cell proliferation and metabolism. The expression of many metabolic genes is antiphasic to cell cycle-related genes, the former peaking during the day and the latter at night. Consistently, accumulation of reactive oxygen species, a byproduct of oxidative phosphorylation, and S-phase are antiphasic to each other in telogen skin. Furthermore, the circadian variation in S-phase is controlled by BMAL1 intrinsic to keratinocytes, because keratinocyte-specific deletion of Bmal1 obliterates time-of-day-dependent synchronicity of cell division in the epidermis leading to a constitutively elevated cell proliferation. In agreement with higher cellular susceptibility to UV-induced DNA damage during S-phase, we found that mice are most sensitive to UVB-induced DNA damage in the epidermis at night. Because in the human epidermis maximum numbers of keratinocytes go through S-phase in the late afternoon, we speculate that in humans the circadian clock imposes regulation of epidermal cell proliferation so that skin is at a particularly vulnerable stage during times of maximum UV exposure, thus contributing to the high incidence of human skin cancers.Arntl gene | circadian rhythm | UVB damage | cell cycle T he highly conserved circadian clock regulates organismal adaptation to the light:dark (LD) cycles caused by the rotation of the Earth (1). Located in the suprachiasmatic nucleus of the vertebrate hypothalamus, the central clock is an intrinsic pacemaker with a spontaneous firing rate and a nearly 24-h rhythmic gene expression. This central pacemaker is thought to synchronize peripheral clocks found in the vast majority of tissues and cells. The core circadian clock machinery is composed of the heterodimeric bHLH-PAS transcription factors CLOCK and BMAL1 that bind E-box elements to activate clock-controlled genes, as well as Period (Per1, 2, and 3) and Cryptochrome (Cry1 and 2). PERs and CRYs inhibit CLOCK/BMAL1 activity upon their translocation into the nucleus, thus constituting a negative arm in the circadian feedback loop. CLOCK/ BMAL1 also activate expression of nuclear receptors ROR and REV-ERBα, which in turn respectively activate and inhibit the transcription of Bmal1 and other target genes containing retinoic acid-related orphan receptor response elements.Although the circadian clock is active in most mammalian tissues, the battery of genes under circadian regulation is largely tissue specific (2), suggesting that the circadian clock modulates physiological processes unique to each organ. Here we have focused on the role of the clock within skin, an organ dominated on the one hand by the cycling hair follicles and on the other by the continuously r...

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Section: Discussionsupporting

confidence: 77%

Brain and muscle Arnt-like protein-1 (BMAL1) controls circadian cell proliferation and susceptibility to UVB-induced DNA damage in the epidermis

Geyfman¹,

Kumar

Liu³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

223

322

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“…These data suggest that it may be possible for the cell-cycle rhythm to be entrained to 24-h fluctuations in temperature in a rhythmic host environment. Discussion DNA synthesis, mitosis, and the expression of cell-cycle proteins in mammalian tissues (e.g., skin, bone marrow, gut, tongue, and oral mucosa) occur with a 24-h cycle in vivo (3)(4)(5)(49)(50)(51)(52)(53)(54)(55) and circadian periodicity of cell mitosis persists in rodents in constant darkness (2,5). Daily rhythms of cell-cycle protein expression (Cyclins E, A, and B1) were also observed in human oral epithelium sampled by biopsy at 4-h intervals for 24 h from healthy human subjects (3).…”

Section: Resultsmentioning

confidence: 99%

“…Because cell division is critical to the survival of unicellular organisms and the integrity of DNA is susceptible to UV irradiation, the progression of the cell cycle was probably also strongly affected by daily changes in the environment. Indeed, multiple studies have measured diurnal fluctuations in cell division such that mitosis occurs at a specific time of day in numerous species ranging from unicellular organisms (2) to humans (3)(4)(5). These data suggest that the circadian and cell cycles may be coupled in vivo.…”

mentioning

confidence: 99%

Circadian-independent cell mitosis in immortalized fibroblasts

Yeom

Pendergast

Ohmiya

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Two prominent timekeeping systems, the cell cycle, which controls cell division, and the circadian system, which controls 24-h rhythms of physiology and behavior, are found in nearly all living organisms. A distinct feature of circadian rhythms is that they are temperaturecompensated such that the period of the rhythm remains constant (∼24 h) at different ambient temperatures. Even though the speed of cell division, or growth rate, is highly temperature-dependent, the cell-mitosis rhythm is temperature-compensated. Twenty-fourhour fluctuations in cell division have also been observed in numerous species, suggesting that the circadian system is regulating the timing of cell division. We tested whether the cell-cycle rhythm was coupled to the circadian system in immortalized rat-1 fibroblasts by monitoring cell-cycle gene promoter-driven luciferase activity. We found that there was no consistent phase relationship between the circadian and cell cycles, and that the cell-cycle rhythm was not temperature-compensated in rat-1 fibroblasts. These data suggest that the circadian system does not regulate the cell-mitosis rhythm in rat-1 fibroblasts. These findings are inconsistent with numerous studies that suggest that cell mitosis is regulated by the circadian system in mammalian tissues in vivo. To account for this discrepancy, we propose two possibilities: (i) There is no direct coupling between the circadian rhythm and cell cycle but the timing of cell mitosis is synchronized with the rhythmic host environment, or (ii) coupling between the circadian rhythm and cell cycle exists in normal cells but it is disconnected in immortalized cells.O rganization of physiology and behavior into specific time domains is a fundamental property of nearly all living organisms. Anticipation of periodic changes in the environment presumably increased survival and reinforced the development of endogenous circadian oscillators (1). Because cell division is critical to the survival of unicellular organisms and the integrity of DNA is susceptible to UV irradiation, the progression of the cell cycle was probably also strongly affected by daily changes in the environment. Indeed, multiple studies have measured diurnal fluctuations in cell division such that mitosis occurs at a specific time of day in numerous species ranging from unicellular organisms (2) to humans (3-5). These data suggest that the circadian and cell cycles may be coupled in vivo.Circadian rhythms are self-sustained oscillations in physiology and behavior with endogenous periods of ≈24 h that can be synchronized, or entrained, to environmental cues such as the light/dark cycle or temperature (6). In mammals, the master circadian clock is located in the suprachiasmatic nuclei (SCN) of the anterior hypothalamus. Genes that are important for circadian timekeeping are expressed not only in the SCN but also in many peripheral tissues, including fibroblasts (7-11). Immortalized embryonic fibroblasts exhibit circadian rhythms of gene expression (12) and, using singlecell imaging...

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“…Los genes reloj en su oscilación rítmica ejercen influencia sobre el control de otros procesos al nivel molecular, en particular, sobre los estadios del ciclo celular, la apoptosis y la reparación del ADN en las células (2,16). Estudios en cianobacterias, plantas, vertebrados (15,17) y humanos (18) han mostrado que los componentes de los ritmos circadianos regulan diferentes genes del ciclo celular, incluyendo c-myc, wee1, p21 y las ciclinas, que permiten la transición de la célula a través del ciclo celular (16,19,20).…”

Section: Regulación Del Ciclo Celular Por El Reloj Biológico Endógenounclassified

“…Estudios en cianobacterias, plantas, vertebrados (15,17) y humanos (18) han mostrado que los componentes de los ritmos circadianos regulan diferentes genes del ciclo celular, incluyendo c-myc, wee1, p21 y las ciclinas, que permiten la transición de la célula a través del ciclo celular (16,19,20).…”

Section: Regulación Del Ciclo Celular Por El Reloj Biológico Endógenounclassified

Los ritmos circadianos en cáncer y la cronoterapia

Molina-Rodríguez¹,

Álvarez²

2016

iatreia

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RESUMENLos ritmos circadianos, períodos fisiológicos de 24 horas aproximadamente, coordinan la actividad temporal de la mayoría, si no, de todos los seres vivos del planeta. Uno de los procesos más importantes del cuerpo, la proliferación celular, también está regulado por el reloj biológico cuya alteración puede tener repercusiones directas en el desarrollo del cáncer. El concepto de cronoterapia ha surgido a partir de la evidencia que tanto la proliferación de las células, como los mecanismos responsables de la farmacocinética y la farmacodinamia de los antineoplásicos ocurren a horas específicas del día. En esta revisión se presentan las generalidades del ciclo circadiano y su relación con el ciclo celular y el cáncer. Además, se expone evidencia del uso de la cronoterapia en pacientes con leucemia linfocítica aguda y en estudios clínicos de cáncer de colon, endometrio y ovario con asignación aleatoria. Se concluye que la hora de administración de la quimioterapia debe tener en cuenta los ritmos circadianos de los pacientes. Se enfatiza en la necesidad de hacer estudios clínicos enfocados en la quimioterapia cronomodulada, con el fin de aumentar la tolerancia y efectividad de los medicamentos con los protocolos existentes.

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Circadian rhythm of cell division

Cited by 41 publications

References 110 publications

Brain and muscle Arnt-like protein-1 (BMAL1) controls circadian cell proliferation and susceptibility to UVB-induced DNA damage in the epidermis

Brain and muscle Arnt-like protein-1 (BMAL1) controls circadian cell proliferation and susceptibility to UVB-induced DNA damage in the epidermis

Circadian-independent cell mitosis in immortalized fibroblasts

Los ritmos circadianos en cáncer y la cronoterapia

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