Cisplatin-DNA Adduct Repair of Transcribed Genes is Controlled by Two Circadian Programs in Mouse Tissues
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ABSTRACT:
PROVIDER: PRJNA432384 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6659140.fastq.gz | Fastqsanger.gz | |||
| SRR6659150.fastq.gz | Fastqsanger.gz | |||
| SRR6659131.fastq.gz | Fastqsanger.gz | |||
| SRR6659141.fastq.gz | Fastqsanger.gz | |||
| SRR6659151.fastq.gz | Fastqsanger.gz |
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Project description:We tested the impact of clock time on excision repair of cisplatin-induced DNA damage at single nucleotide resolution across the genome in mouse liver and kidney. We found that genome repair is controlled by two circadian programs.
2018-06-21 | GSE109938 | GEO
Project description:Cisplatin is the most commonly used chemotherapeutic drug for treating solid tumors. However, its toxicity and the innate or acquired resistance of cancer cells to the drug limit its usefulness. Cisplatin kills cells by forming cisplatin-DNA adducts, most commonly in the form of Pt-d(GpG) diadduct. We recently showed that repair of this adduct within 2 hours following injection is controlled by two circadian programs: (1) The circadian clock controls transcription of 2000 genes in mouse liver and thereby controls repair of the transcribed strand of these genes via transcription coupled repair in a rhythmic fashion unique to each gene’s phase of transcription. (2) The basal excision repair activity itself is controlled by the circadian clock with a single phase at which the repair of the non-transcribed strand and the rest of the genome take place. Here, we have followed the repair kinetic for long periods genome-wide both globally and at single nucleotide resolution by the Excision Repair-sequencing (XR-seq) method to gain further insight into cisplatin DNA damage and repair with the aim of improving the therapeutic index of the drug. Our data show that transcription-driven repair is complete after two days, while completion of basal repair of nontranscribed strands, silent genes and intergenic regions requires weeks. In rhythmically controlled genes, oscillations of transcribed repair are observed up to 2 days post-injection, and in both constitutively transcribed and rhythmic genes, we see a trend in template strand repair with time from the 5’to 3’ end. These findings add to the complexity of circadian- and transcription-dependent and -independent control of repair exhibited by this model organism in response to cisplatin.
2019-06-24 | GSE132002 | GEO
Project description:Cisplatin is the most commonly used chemotherapeutic drug for treating solid tumors. However, its toxicity and the innate or acquired resistance of cancer cells to the drug limit its usefulness. Cisplatin kills cells by forming cisplatin-DNA adducts, most commonly in the form of Pt-d(GpG) diadduct. We recently showed that repair of this adduct within 2 hours following injection is controlled by two circadian programs: (1) The circadian clock controls transcription of 2000 genes in mouse liver and thereby controls repair of the transcribed strand of these genes via transcription coupled repair in a rhythmic fashion unique to each gene’s phase of transcription. (2) The basal excision repair activity itself is controlled by the circadian clock with a single phase at which the repair of the non-transcribed strand and the rest of the genome take place. Here, we have followed the repair kinetic for long periods genome-wide both globally and at single nucleotide resolution by the Excision Repair-sequencing (XR-seq) method to gain further insight into cisplatin DNA damage and repair with the aim of improving the therapeutic index of the drug. Our data show that transcription-driven repair is complete after two days, while completion of basal repair of nontranscribed strands, silent genes and intergenic regions requires weeks. In rhythmically controlled genes, oscillations of transcribed repair are observed up to 2 days post-injection, and in both constitutively transcribed and rhythmic genes, we see a trend in template strand repair with time from the 5’to 3’ end. These findings add to the complexity of circadian- and transcription-dependent and -independent control of repair exhibited by this model organism in response to cisplatin.
2019-06-24 | GSE132993 | GEO
Project description:Cisplatin is a major cancer chemotherapeutic drug. It kills cancer cells by damaging their DNA, mainly in the form of Pt-d(GpG) diadducts. However, it also has serious side effects, including nephrotoxicity and hepatotoxicity that limit its usefulness. Chronotherapy is taking circadian time into account during therapy to improve the therapeutic index, by improving efficacy and/or limiting toxicity. To this end, we tested the impact of clock time on excision repair of cisplatin-induced DNA damage at single-nucleotide resolution across the genome in mouse kidney and liver. We found that genome repair is controlled by two circadian programs. Repair of the transcribed strand (TS) of active, circadian-controlled genes is dictated by each gene's phase of transcription, which falls across the circadian cycle with prominent peaks at dawn and dusk. In contrast, repair of the nontranscribed strand (NTS) of all genes, repair of intergenic DNA, and global repair overall peaks at Zeitgeber time ZT08, as basal repair capacity, which is controlled by the circadian clock, peaks at this circadian time. Consequently, the TS and NTS of many genes are repaired out of phase. As most cancers are thought to have defective circadian rhythms, these results suggest that future research on timed dosage of cisplatin could potentially reduce damage to healthy tissue and improve its therapeutic index.
| S-EPMC6003508 | biostudies-literature
Project description:We used the recently developed Excision Repair-sequencing (XR-seq) method to study genome-wide repair of UV-induced DNA damage in Arabidopsis. We found that the repair of cyclobutane pyrimidine dimers for a large fraction of the genome is controlled by the joint actions of the circadian clock and transcription by RNA polymerase II. Arabidopsis has a relatively compact genome, and a large fraction of the genes are controlled by the circadian clock. Our data on the interface of these two global regulatory systems reveal very strong repair preference of the transcribed strands of Arabidopsis genes, 10 to 30% of which are circadian time-dependent. Thus, throughout the day, Arabidopsis exhibits enormous dynamic range in repair to cope with exposure to sunlight.
2018-04-17 | GSE108932 | GEO
Project description:Cisplatin is one of the most potent chemotherapy drugs to treat cancers, but its clinical application remains limited due to severe nephrotoxicity. Several approaches have been developed to minimize such side effects, notably including chronotherapy, a well-known strategy based on the circadian clock. However, the component of the circadian clock machinery that particularly responses to the cisplatin stimulation remains unknown, including its functions in cisplatin-induced renal injury. In our present study, we demonstrated that Bmal1, as a key clock gene, was induced by the cisplatin stimulation in the mouse kidney and cultured human HK-2 renal cells. Gain- and loss-of-function studies indicated that Bmal1 facilitated cisplatin-induced renal injury both in vivo and in vitro, by aggravating the cell apoptotic process. More importantly, RNA-seq analysis revealed that Bmal1 triggered the expression of hallmark genes involved in renal hepatization, a critical event accompanied by the injury. At the molecular level, Bmal1 activated the transcription of hepatization-associated genes through direct recruitment to the E-box motifs of their promoters. Our findings suggest that Bmal1, a pivotal mediator induced renal injury in response to cisplatin treatment, and the therapeutic intervention targeting Bmal1 in the kidney may be a promising strategy to minimize the toxic side-effects of cisplatin in its clinical applications.
2020-04-24 | GSE149172 | GEO
Project description:Microarray expression profiling was used to identify genes expressed in developing soybean (Glycine max) seeds that are controlled by the circadian clock. Plants with developing seeds were entrained to 12hour light: 12 hour dark cycles and sampled in constant light conditions.
2010-06-21 | GSE18827 | GEO
Project description:This randomized pilot trial studies how well two supportive programs work for improving fatigue and depressive symptoms in patients with GI undergoing chemotherapy. Possible mediators such as psychological stress, circadian disruption, and inflammation, will also be explored.
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Project description:Microarray expression profiling was used to identify genes expressed in developing soybean (Glycine max) seeds that are controlled by the circadian clock. Plants with developing seeds were entrained to 12hour light: 12 hour dark cycles and sampled in constant light conditions. Soybean seeds entrained to 12 hour-light:12 hour dark photocycles were harvested after 24 hours of constant light and temperature conditions. Timepoint 24h represents subjective dawn. To minimize developmental variation, flowers were marked as they opened and seeds were harvested from marked pods after 5 weeks. There are two replicate samples at each time point, and each sample consists of 8 seeds collected from three diffferent plants.
2010-07-08 | E-GEOD-18827 | biostudies-arrayexpress
Project description:The circadian clock gene Bmal1 facilitates cisplatin-induced renal injury and hepatization
| PRJNA627591 | ENA