Genome-wide distribution of transcription-coupled nucleotide excision repair and RNA polymerase II in DRB-treated XP-C cells after UV damage
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PROVIDER: PRJNA418134 | ENA |
REPOSITORIES: ENA
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Project description:The fate of RNAPII in the course of the transcription-coupled repair pathway is unclear. To address this problem we have used methods to control transcription, so as to initiate a discrete ‘wave’ of elongation complexes. We also used methods to identify where elongation complexes and transcription-repair coupling events are located in genes throughout the genome.
2017-12-21 | GSE106823 | 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:XPA is required for Nucleotide Excision Repair system, which could function to repair DNA damage induced by the UV. UV damage on the genomic DNA cannot be removed, thus persistence of damage could affect the transcriptional machinary. We used the microarray to investigate the global expression profiles in the XP-A and XP-V cells in the low dose of UVC comparing with fibroblast from healthy person. Human primary fibroblasts were developed from the skin of healthy person and two XP patients (XP-A and XP-V). We evaluated global expression profiles comparing the UVC-exposed (0.5J/m2, 5J/m2) with non-exposed sample.
2015-07-14 | E-GEOD-70818 | biostudies-arrayexpress
Project description:XPA is required for Nucleotide Excision Repair system, which could function to repair DNA damage induced by the UV. UV damage on the genomic DNA cannot be removed, thus persistence of damage could affect the transcriptional machinary. We used the microarray to investigate the global expression profiles in the XP-A and XP-V cells in the low dose of UVC comparing with fibroblast from healthy person.
2015-07-14 | GSE70818 | 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:XPA is a central scaffold protein in nucleotide excision repair (NER) that interacts with and coordinates the assembly of repair complexes. Inactivating mutations in XPA causes Xeroderma Pigmentosum (XP), which is characterized by extreme UV sensitivity and a highly elevated skin cancer risk. Here, we describe two Dutch siblings in their late forties carrying a homozygous H244R substitution in the C-terminus of XPA with a mild manifestation of XP without skin cancer, but with neurological features including cerebellar ataxia. We show that the mutant XPA protein shows a severely weakened interaction with the TFIIH complex leading to its inefficient association with NER complexes and an inability to support the efficient association of the ERCC1-XPF endonuclease with repair complexes. Despite these defects, we find that patient-derived fibroblasts and reconstituted knockout cells carrying the H244R substitution show considerable levels of residual global genome repair (~40%), which is in intrinsic property of the mutated protein as revealed by in vitro experiments. In contrast, patient fibroblasts and engineered cells only expressing the mutant XPA protein were fully deficient in transcription-coupled repair. We report a new case of XPA deficiency that interferes with TFIIH binding and primarily affects the transcription-coupled sub-pathway of nucleotide excision repair, which is more closely associated with neurological features than to skin abnormalities.
2023-02-19 | PXD033520 | Pride
Project description:Xeroderma Pigmentosum (XP) is a DNA repair disorder characterized by photosensitivity, resulting in occurrence of freckle-like pigmented maculae and depigmented maculae on sun-exposed areas. XP complementation group A (XP-A) is the most frequent type in Japan, and patients with XP-A present most severe cutaneous and neurological symptoms due to nucleotide excision repair deficiency. Here, we established induced pluripotent stem cells (iPSCs) derived from XP-A patients and successfully differentiated into melanocytes. To elucidate the pathophysiology of XP, we comprehensively analyzed the difference in gene expression between XP-A-iMCs and healthy-control-iPSC-derived melanocytes (HC-iMCs) 4 hours and 12 hours after irradiation with 30 J/m2 or 150 J/m2 of UV-B using microarray analysis.
2022-01-01 | GSE185308 | GEO
Project description:Repair of UV damage from the transcribed strand (TS) of yeast genes is rapid due to the transcription coupled nucleotide excision repair (TC-NER) pathway. TC-NER is triggered when RNA polymerase stalls at UV damage, such as a UV-induced cyclobutane pyrimidine dimer (CPD). During transcription, the histone methyltransferase Set2 methylates histone H3K36, but it is not known if Set2 regulates TC-NER. Here, we report genome-wide repair maps of UV-induced cyclobutane pyrimidine dimers (CPDs) in yeast cells lacking Set2.
2022-02-21 | GSE179794 | GEO
Project description:We characterized the role of H3K36 methylation in regulating repair of UV damage from the transcribed strand (TS) of yeast genes by the transcription coupled nucleotide excision repair (TC-NER) pathway. TC-NER is triggered when RNA polymerase stalls at UV damage, such as a UV-induced cyclobutane pyrimidine dimer (CPD). During transcription, the histone methyltransferase Set2 methylates histone H3K36, but it is not known if H3K36 methylation regulates TC-NER. Here, we report genome-wide repair maps of UV-induced cyclobutane pyrimidine dimers (CPDs) in yeast cells containing mutants in histone H3K36 (or set2).
2022-02-21 | GSE194101 | GEO
Project description:Embryonic stem cells can self-renew and differentiate, holding great promise for regenerative medicine. They also employ multiple mechanisms to preserve the integrity of their genomes. Nucleotide excision repair, a versatile repair mechanism, removes bulky DNA adducts from the genome. However, the dynamics of the capacity of nucleotide excision repair during stem cell differentiation remain unclear. Here, using immunoslot blot assay, we measured repair rates of UV-induced DNA damage during differentiation of human embryonic carcinoma (NTERA-2) cells into neurons and muscle cells. Our results revealed that the capacity of nucleotide excision repair increases as cell differentiation progresses. We also found that inhibition of the apoptotic signaling pathway has no effect on nucleotide excision repair capacity. Furthermore, RNA-seq-based transcriptomic analysis indicated that expression levels of four core repair factors, xeroderma pigmentosum (XP) complementation group A (XPA), XPC, XPG, and XPF-ERCC1, are progressively up-regulated during differentiation, but not those of replication protein A (RPA) and transcription factor IIH (TFIIH). Together, our findings reveal that increase of nucleotide excision repair capacity accompanies cell differentiation, supported by the up-regulated transcription of genes encoding DNA repair enzymes during differentiation of two distinct cell lineages.
2019-03-07 | GSE125370 | GEO