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Circadian Cryptochrome 1 (CRY1) Rhythmically Modulates the DNA Damage Response

ABSTRACT: Circadian Cryptochrome 1 (CRY1) Rhythmically Modulates the DNA Damage Response

PROVIDER: PRJNA605447 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11041338.fastq.gz	Fastqsanger.gz
	SRR11041339.fastq.gz	Fastqsanger.gz
	SRR11041340.fastq.gz	Fastqsanger.gz
	SRR11041341.fastq.gz	Fastqsanger.gz
	SRR11041342.fastq.gz	Fastqsanger.gz

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Circadian Cryptochrome 1 (CRY1) Rhythmically Modulates the DNA Damage Response [ChIP-seq]

Project description:Circadian Cryptochrome 1 (CRY1) Rhythmically Modulates the DNA Damage Response [ChIP-seq]

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Circadian Cryptochrome 1 (CRY1) Rhythmically Modulates the DNA Damage Response [RNA-seq]

Project description:Circadian Cryptochrome 1 (CRY1) Rhythmically Modulates the DNA Damage Response [RNA-seq]

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Circadian Cryptochrome 1 (CRY1) Rhythmically Modulates the DNA Damage Response [RNA-seq]

Project description:These studies identify a novel node of AR-regulated DNA repair through CRY1 directly regulating HR-mediated DNA repair to enhance cancer progression and discern a potential avenue to be targeted in late stage disease to improve patient outcome.

2020-11-24 | GSE144961 | GEO

Circadian Cryptochrome 1 (CRY1) Rhythmically Modulates the DNA Damage Response [ChIP-seq]

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A repeatedly evolved mutation in Cryptochrome-1 of subterranean animals alters behavioral and molecular circadian rhythms

Project description:The repeated evolution of similar phenotypes in independent lineages often occurs in response to similar environmental pressures, through similar or different molecular pathways. Recently, a repeatedly occurring mutation R263Q in a conserved domain of the protein Cryptochrome-1 (CRY1) was reported in multiple species inhabiting subterranean environments. Cryptochromes regulate circadian rhythms, and glucose and lipid metabolism. Subterranean species show changes to their circadian rhythm and metabolic pathways, making it likely that this mutation in CRY1 contributes to adaptive phenotypic changes. To identify the functional consequences of the CRY1 R263Q mutation, we generated a mouse model homozygous for this mutation. Indirect calorimetry experiments revealed delayed locomotor activity, energy expenditure and feeding patterns of mutant mice in the dark phase, but no further metabolic phenotypes – unlike a full loss of function of CRY1. Gene expression analyses showed altered expression of several canonical circadian genes in the livers of the mutant mice, fortifying the notion that CRY1 R263Q impacts metabolism. Our data provide the first characterization of a novel mutation that has repeatedly evolved in subterranean environments, supporting the idea that shared environmental constraints can drive the evolution of similar phenotypes through similar genetic changes.

2025-07-23 | GSE277611 | GEO

AP-MS of small molecule that selectively destabilizes Cryptochrome 1

Project description:Cryptochromes are negative transcriptional regulators of the circadian clock in mammals. It is not clear how reducing the level of endogenous CRY1 in mammals will affect circadian rhythm and the relation of such a decrease with apoptosis. Here, we discovered a molecule (M47) that destabilizes Cryptochrome 1 (CRY1) both in vitro and in vivo. The M47 selectively enhanced the degradation rate of CRY1 by increasing its ubiquitination and resulted in increasing the circadian period length of U2OS Bmal1-dLuc cells. In addition, subcellular fractionation studies from mice liver indicated that M47 increased degradation of the CRY1 in the nucleus. Furthermore, M47-mediated CRY1 reduction enhanced cisplatin-induced apoptosis in Ras-transformed p53 null fibroblast cells. Systemic repetitive administration of M47 increased the median lifespan of p53-/- mice by ~25%. Collectively our data suggest that M47 is a very promising molecule to treat forms of cancer depending on the p53 mutation.

2022-11-07 | PXD037311 | Pride

Transcriptional Repressor Gm129 Modulates the Circadian Gene Expression by Inhibiting CLOCK:BMAL1 Activity

Project description:The mammalian circadian clock is a molecular oscillator composed of a feedback loop that involves transcriptional activators CLOCK and BMAL1, and repressors Cryptochrome (CRY) and Period (PER). Here we show that a direct CLOCK-BMAL1 target gene, Gm129, is a novel regulator of the feedback loop. ChIP analysis revealed that the CLOCK:BMAL1:CRY1 complex strongly occupies the promoter region of Gm129. Both mRNA and protein levels of GM129 exhibit high amplitude circadian oscillations in mouse liver, and Gm129 gene encodes a nuclear-localized protein that directly interacts with BMAL1 and represses CLOCK:BMAL1 activity. In vitro and in vivo protein-DNA interaction results demonstrate that, like CRY1, GM129 functions as a repressor by binding to the CLOCK:BMAL1 complex on DNA. Although Gm129-/- or Cry1-/- Gm129-/- mice retain a robust circadian rhythm, the peaks of Nr1d1 and Dbp mRNAs in liver exhibit significant phase delay compared to control. Our results suggest that, in addition to CRYs and PERs, GM129 protein contributes to the transcriptional feedback loop by modulating CLOCK:BMAL1 activity as a transcriptional repressor. Examination of 3 transcriptional regulators in mouse liver

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Circadian Cryptochrome 1 (CRY1) Rhythmically Modulates the DNA Damage Response

Project description:This SuperSeries is composed of the SubSeries listed below.

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Duper is a Cryptochrome 1 null mutation in Syrian hamsters

Project description:The duper mutation is a recessive mutation that shortens the period length of the circadian rhythm in Syrian hamsters. These animals show a large phase shift when responding to light pulses. Using two distinct ecotypes and a fast homozygosity mapping strategy, we identified duper as an early nonsense allele of Cryptochrome 1 (Cry1) leading to a short, unstable protein.

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Gene Model 129 (Gm129) Encodes a Novel Transcriptional Repressor that Modulates Circadian Gene Expression

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