Excision repair hotspots of UV-induced DNA damage in the human genome
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ABSTRACT:
PROVIDER: PRJNA623860 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11510187.fastq.gz | Fastqsanger.gz | |||
| SRR11510188.fastq.gz | Fastqsanger.gz | |||
| SRR11510189.fastq.gz | Fastqsanger.gz | |||
| SRR11510190.fastq.gz | Fastqsanger.gz |
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Project description:We recently developed high-throughput sequencing approaches, eXcision Repair sequencing (XR-seq) and Damage-seq, to generate genome-wide mapping of DNA damage formation and excision repair, respectively, with single-nucleotide resolution. Here, we adopted time-course XR-seq data to profile UV-induced excision repair dynamics, paired with Damage-seq data to quantify the overall induced DNA damage. We identified genome-wide repair hotspots that are subject to exemplified amount of repair very soon after UV irradiation. We show that such repair hotspots do not result from hypersensitivity to DNA damage and are thus not damage hotspots. We find that the earliest repair occur preferentially in promoters and enhancers from open-chromatin regions. The repair hotspots are also significantly enriched for frequently interacting regions and super-enhancers, both of which are hotspots for local chromatin interactions. We further extend the interrogation of chromatin organization to DNA replication timing and conclude that early-repair hotspots are enriched for early-replication domains. Collectively, we report genome-wide early-repair hotspots of UV-induced damage, in association with chromatin states and epigenetic compartmentalization of the human genome.
2020-04-09 | GSE148303 | GEO
Project description:We developed a method for genome-wide mapping of DNA excision repair named XR-seq (eXcision Repair-seq). Human nucleotide excision repair generates two incisions surrounding the site of damage, creating a ~30-mer. In XR-seq, this fragment is isolated and subjected to high-throughput sequencing. We used XR-seq to produce stranded, nucleotide-resolution maps of repair of two UV-induced DNA damages in human cells, cyclobutane pyrimidine dimers (CPDs) and (6-4) pyrimidine-pyrimidone photoproducts ((6-4)PPs). In wild-type cells, CPD repair was highly associated with transcription, specifically with the template strand. Experiments in cells defective in either transcription-coupled excision repair or general excision repair isolated the contribution of each pathway to the overall repair pattern, and showed that transcription-coupled repair of both photoproducts occurs exclusively on the template strand. XR-seq maps capture transcription-coupled repair at sites of divergent gene promoters and bi-directional eRNA production at enhancers. XR-seq data also uncovered the repair characteristics and novel sequence preferences of CPDs and (6-4)PPs. XR-seq and the resulting repair maps will facilitate studies of the effects of genomic location, chromatin context, transcription, and replication on DNA repair in human cells. We have performed XR-seq for two types of UV-induced damages (CPD and (6-4)PP) in three different cell lines: NHF1, XP-C (XP4PA-SV-EB, GM15983)), and CS-B (CS1ANps3g2, GM16095). Two biological replicates were performed for each experiment, in which independent cell populations were UV treated and subjected to XR-seq.
2015-04-19 | E-GEOD-67941 | biostudies-arrayexpress
Project description:UV-induced DNA lesions are an important contributor to mutagenesis and cancer, but it is not fully understood how the chromosomal landscape influences UV lesion formation and repair. We have used a novel high-throughput sequencing method to precisely map UV-induced cyclobutane pyrimidine dimers (CPDs) at nucleotide resolution throughout the yeast genome. Analysis of CPD formation reveals that nucleosomal DNA having an inward rotational setting is protected from CPD lesions. In strongly positioned nucleosomes, this nucleosome 'photofootprint' overrides intrinsic dipyrimidine sequence preferences for CPD formation. CPD formation is also inhibited by DNA-bound transcription factors, in effect protecting important DNA elements from UV damage. Analysis of CPD repair revealed a clear signature of efficient transcription-coupled nucleotide excision repair. Repair was less efficient at translational positions near a nucleosome dyad and at heterochromatic regions in the yeast genome. These findings define the roles of nucleosomes and transcription factors in UV damage formation and repair. UV mapping data was analyzed for yeast cells irradiated with 125J/m2 and allowed to repair for 0hr (2 samples), 20 minutes, 1 hour, or 2 hours. Data is also included for naked DNA irradiated with UV 60 or 90 J/m2
2016-08-19 | E-GEOD-79977 | biostudies-arrayexpress
Project description:DNA base damage arises frequently in all living cells and is an important contributor to mutations and genome instability. The main repair pathway for base damage is base excision repair (BER). How the formation and repair of base lesions are modulated by DNA-binding proteins is poorly understood. Here we used a high-throughput damage mapping method, N-methylpurine-sequencing (NMP-seq), to characterize alkylation damage distribution and BER at yeast transcription factor (TF) binding sites upon the treatment with alkylating agent methyl methanesulfonate (MMS). We found that formation of alkylation damage was mainly suppressed at the binding sites of yeat TFs Abf1 and Reb1, but individual hotspots with elevated damage formation were also observed. Furthermore, our data indicates that repair of alkyhlation damage by BER was significantly inhibited both within the TF core motif and its adajcent DNA. The modulation of damage formation and BER was caused by the TF binding, because lesion formation and repair can be restored by depletion of Abf1 or Reb1 from the nucleus. Finally, we show that repair of UV damage by nucleotide excision repair (NER) was also inhibited at the binding sites of Abf1 and Reb1. A comparision between alkylyation and UV damage repair reveals that NER was inhibited in a broader DNA region relative to BER. Thus, our analyses indicate that TF binding significantly modulates alkylation damage formation and inhibits repair by the BER pathway. The interplay between base damage formation and BER may play an important role in affecting mutation frequency in gene regulatory regions.
2021-12-31 | GSE183622 | GEO
Project description:UV-induced DNA damage is the major carcinogen of skin cancer. We developed HS-Damage-seq to map UV damage with unprecedented sensitivity and resolution in human cells. While the distribution of UV-induced damage are mainly determined by sequence context and essentially uniform throughout the genome, transcription factors can affect damage formation at specific positions. With time-course experiments, we observed changes in damage distribution at particular genomic loci and chromatin states, which reflects the nucleotide excision repair preferences and complements the repair maps by XR-seq. Our results demonstrated that while initial damage is uniformly distributed, they are heterogeneously repaired throughout the genome. The combination of damage and repair maps provides a holistic perspective of UV damage and repair in the human genome.
2017-06-27 | GSE98025 | GEO
Project description:We report the application of single-molecule-based sequencing technology (XR-seq) for high-throughput profiling of nucleotide excision repair in Drosophila four developmental stages and S2 cells. By obtaining over six billion bases of sequence from UV and cisplatin damage antibodies immunoprecipitated excision DNA, we generated genome-wide nucleotide excision repair maps of Drosophila Embryo, Larva, Pupa , two gender of adults and S2 cells . We find that Drosophila performs transcription-coupled repair (TCR) at all its developmental stages. S2 cell carry out TCR response to both UV and Cisplatin damage. Finally, we show that XPC repair factor is required for both global and transcription-coupled repair in Drosophila. This study provides the mechanism of nucleotide excision repair of Drosophila in vivo and vitro response to UV and Cisplatin damage.
2022-02-25 | GSE184926 | GEO
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:We developed a method for genome-wide mapping of DNA excision repair named XR-seq (eXcision Repair-seq). Human nucleotide excision repair generates two incisions surrounding the site of damage, creating a ~30-mer. In XR-seq, this fragment is isolated and subjected to high-throughput sequencing. We used XR-seq to produce stranded, nucleotide-resolution maps of repair of two UV-induced DNA damages in human cells, cyclobutane pyrimidine dimers (CPDs) and (6-4) pyrimidine-pyrimidone photoproducts ((6-4)PPs). In wild-type cells, CPD repair was highly associated with transcription, specifically with the template strand. Experiments in cells defective in either transcription-coupled excision repair or general excision repair isolated the contribution of each pathway to the overall repair pattern, and showed that transcription-coupled repair of both photoproducts occurs exclusively on the template strand. XR-seq maps capture transcription-coupled repair at sites of divergent gene promoters and bi-directional eRNA production at enhancers. XR-seq data also uncovered the repair characteristics and novel sequence preferences of CPDs and (6-4)PPs. XR-seq and the resulting repair maps will facilitate studies of the effects of genomic location, chromatin context, transcription, and replication on DNA repair in human cells.
2015-04-19 | GSE67941 | GEO
Project description:To recognize DNA damage, nucleotide excision repair (NER) deploys a multipart mechanism by which the XPC sensor detects helical distortions followed by engagement of TFIIH for lesion verification. Accessory players ensure that this factor handover takes place on chromatin where DNA is wrapped around histones. We show that the histone methyltransferase ASH1L, once activated by MRG15, accelerates global-genome NER activity. Upon UV irradiation, ASH1L deposits H3K4me3 marks all over the genome (except in gene promoters), thus priming chromatin for relocations of XPC from native to damaged DNA. ASH1L further recruits the histone chaperone FACT to UV lesions. In the absence of ASH1L, MRG15 or FACT, XPC persists on damaged DNA without being able to deliver lesions to the TFIIH verifier. We conclude that ASH1L implements repair hotspots whose H3K4me3 and FACT occupancy confers an active promoter-like code and organization of histones that make DNA damage verifiable by the NER machinery.
2023-06-08 | GSE214182 | GEO
Project description:To recognize DNA damage, nucleotide excision repair (NER) deploys a multipart mechanism by which the XPC sensor detects helical distortions followed by engagement of TFIIH for lesion verification. Accessory players ensure that this factor handover takes place on chromatin where DNA is wrapped around histones. We show that the histone methyltransferase ASH1L, once activated by MRG15, accelerates global-genome NER activity. Upon UV irradiation, ASH1L deposits H3K4me3 marks all over the genome (except in gene promoters), thus priming chromatin for relocations of XPC from native to damaged DNA. ASH1L further recruits the histone chaperone FACT to UV lesions. In the absence of ASH1L, MRG15 or FACT, XPC persists on damaged DNA without being able to deliver lesions to the TFIIH verifier. We conclude that ASH1L implements repair hotspots whose H3K4me3 and FACT occupancy confers an active promoter-like code and organization of histones that make DNA damage verifiable by the NER machinery.
2023-06-08 | GSE227007 | GEO