Does evening sun increase the risk of skin cancer?

Mitra, Sankar

doi:10.1073/pnas.1116516108

Cited by 8 publications

(4 citation statements)

References 16 publications

(14 reference statements)

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“…We show that dramatic hair loss resistance in response to ionizing irradiation can be achieved in WT mice simply by timing γ-irradiation treatment to the time of the day with minimal mitotic activity in hair matrixes. These findings parallel daily changes in sensitivity of epidermis to external UV genotoxicity (8,17,27) and can have important implications for designing radiation therapy and possibly chemotherapy protocols. More immediately, radiation treatment can be administered during the mitotic depression phase to minimize hair loss side effect.…”

Section: Diurnal Rhythm Of Genotoxic Sensitivity In Rapidly Proliferasupporting

confidence: 56%

Local circadian clock gates cell cycle progression of transient amplifying cells during regenerative hair cycling

Plikus

Vollmers

Cruz

et al. 2013

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

121

136

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Regenerative cycling of hair follicles offers an unique opportunity to explore the role of circadian clock in physiological tissue regeneration. We focused on the role of circadian clock in actively proliferating transient amplifying cells, as opposed to quiescent stem cells. We identified two key sites of peripheral circadian clock activity specific to regenerating anagen hair follicles, namely epithelial matrix and mesenchymal dermal papilla. We showed that peripheral circadian clock in epithelial matrix cells generates prominent daily mitotic rhythm. As a consequence of this mitotic rhythmicity, hairs grow faster in the morning than in the evening. Because cells are the most susceptible to DNA damage during mitosis, this cycle leads to a remarkable time-of-day-dependent sensitivity of growing hair follicles to genotoxic stress. Same doses of γ-radiation caused dramatic hair loss in wild-type mice when administered in the morning, during mitotic peak, compared with the evening, when hair loss is minimal. This diurnal radioprotective effect becomes lost in circadian mutants, consistent with asynchronous mitoses in their hair follicles. Clock coordinates cell cycle progression with genotoxic stress responses by synchronizing Cdc2/Cyclin B-mediated G 2 /M checkpoint. Our results uncover diurnal mitotic gating as the essential protective mechanism in highly proliferative hair follicles and offer strategies for minimizing or maximizing cytotoxicity of radiation therapies.proliferation | radiation therapy | hair cycle M any biological events are rhythmic at different levels of organization, from cellular to behavioral. Diverse clock mechanisms have evolved to endow such rhythmic events with proper periodicity. The circadian clock helps organisms anticipate predictable daily changes in their environment and to prepare for diurnal and seasonal adaptations. Mechanistically, the circadian clock is based on the autoregulatory gene expression feedback loop in its core consisting of Clock/brain and muscle ARNT-like 1 (Bmal1)/neuronal PAS domain-containing protein 2 transcription factors that induce Period (Per)/Cryptochrome (Cry) genes expression, the protein products of which, in turn, inhibit these factors (1). Through its output mechanisms, the circadian clock generates daily fluctuations in various homeostatic processes (2). In mammals, a "master circadian clock" in the suprachiasmatic nucleus (SCN) uses both direct and indirect mechanisms to generate daily rhythms in several systemic signaling factors. In the peripheral tissues, local circadian clock also orchestrates intrinsic rhythms for their respective functions.We wanted to examine the role of circadian rhythms in hair cycle, which is a complex regenerative process consisting of sequential phases of hair production (anagen), followed by hair follicle inactivity (telogen). The timing of anagen initiation and anagen cessation (also known as catagen) largely determine the length of this cycle. Following anagen initiation, proliferation of epithelial cells and termin...

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Section: Diurnal Rhythm Of Genotoxic Sensitivity In Rapidly Proliferasupporting

confidence: 56%

Local circadian clock gates cell cycle progression of transient amplifying cells during regenerative hair cycling

Plikus

Vollmers

Cruz

et al. 2013

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

121

136

View full text Add to dashboard Cite

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“…Similarly, constitutive activation of BMAL1 in the Per1/2 knockout mice resulted in more clonogenic epidermal SCs ( Janich et al., 2011 ). These molecular changes affected hair growth ( Plikus et al., 2013 , Geyfman et al., 2012 , Gaddameedhi et al., 2011 , Mitra, 2011 ). Indeed after shaving, older adult PTEN mice displayed a halt in hair growth.…”

Section: Discussionmentioning

confidence: 99%

PTEN Mediates Activation of Core Clock Protein BMAL1 and Accumulation of Epidermal Stem Cells

et al. 2017

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SummaryTissue integrity requires constant maintenance of a quiescent, yet responsive, population of stem cells. In the skin, hair follicle stem cells (HFSCs) that reside within the bulge maintain tissue homeostasis in response to activating cues that occur with each new hair cycle or upon injury. We found that PTEN, a major regulator of the PI3K-AKT pathway, controlled HFSC number and size in the bulge and maintained genomically stable pluripotent cells. This regulatory function is central for HFSC quiescence, where PTEN-deficiency phenotype is in part regulated by BMAL1. Furthermore, PTEN ablation led to downregulation of BMI-1, a critical regulator of adult stem cell self-renewal, and elevated senescence, suggesting the presence of a protective system that prevents transformation. We found that short- and long-term PTEN depletion followed by activated BMAL1, a core clock protein, contributed to accumulation of HFSC.

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“…The rate-limiting factor of NER is XPA that verifies the damage and leads to the recruitment of the incision proteins. The expression of XPA is controlled by the circadian clock which is higher in daytime than at night with clock circadian regulator-aryl hydrocarbon receptor nuclear translocator-like protein (Clock-Bmal1) transcriptional activator and a cryptochrome circadian regulator-period circadian regulator (CRY-PER) transcriptional repressor to enable repair in UV-exposed cells [16]. Its expression is also regulated by other transcription factors including hypoxia-inducible factor 1 (HIF1A) that upregulates XPA expression and high-mobility group protein A1 (HMGA1) that downregulates XPA expression [17, 18].…”

Section: Nucleotide Excision Repair (Ner)mentioning

confidence: 99%

Signaling Pathways, Chemical and Biological Modulators of Nucleotide Excision Repair: The Faithful Shield against UV Genotoxicity

Kobaisi

Fayyad

Rezvani

et al. 2019

Oxidative Medicine and Cellular Longevity

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The continuous exposure of the human body’s cells to radiation and genotoxic stresses leads to the accumulation of DNA lesions. Fortunately, our body has several effective repair mechanisms, among which is nucleotide excision repair (NER), to counteract these lesions. NER includes both global genome repair (GG-NER) and transcription-coupled repair (TC-NER). Deficiencies in the NER pathway underlie the development of several DNA repair diseases, such as xeroderma pigmentosum (XP), Cockayne syndrome (CS), and trichothiodystrophy (TTD). Deficiencies in GG-NER and TC-NER render individuals to become prone to cancer and neurological disorders, respectively. Therefore, NER regulation is of interest in fine-tuning these risks. Distinct signaling cascades including the NFE2L2 (NRF2), AHR, PI3K/AKT1, MAPK, and CSNK2A1 pathways can modulate NER function. In addition, several chemical and biological compounds have proven success in regulating NER’s activity. These modulators, particularly the positive ones, could therefore provide potential treatments for genetic DNA repair-based diseases. Negative modulators, nonetheless, can help sensitize cells to killing by genotoxic chemicals. In this review, we will summarize and discuss the major upstream signaling pathways and molecules that could modulate the NER’s activity.

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Does evening sun increase the risk of skin cancer?

Cited by 8 publications

References 16 publications

Local circadian clock gates cell cycle progression of transient amplifying cells during regenerative hair cycling

Local circadian clock gates cell cycle progression of transient amplifying cells during regenerative hair cycling

PTEN Mediates Activation of Core Clock Protein BMAL1 and Accumulation of Epidermal Stem Cells

Signaling Pathways, Chemical and Biological Modulators of Nucleotide Excision Repair: The Faithful Shield against UV Genotoxicity

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