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DisGeNET5_gene_disease

{"project":"DisGeNET5_gene_disease","denotations":[{"id":"10390531-5#102#121#gene100","span":{"begin":1003,"end":1022},"obj":"gene100"},{"id":"10390531-5#46#48#diseaseC0009207","span":{"begin":947,"end":949},"obj":"diseaseC0009207"}],"relations":[{"id":"102#121#gene10046#48#diseaseC0009207","pred":"associated_with","subj":"10390531-5#102#121#gene100","obj":"10390531-5#46#48#diseaseC0009207"}],"text":"Cells from XP-D and XP-D-CS patients exhibit equally inefficient repair of UV-induced damage in transcribed genes but different capacity to recover UV-inhibited transcription.\nXeroderma pigmentosum (XP) is a rare hereditary human disorder clinically associated with severe sun sensitivity and predisposition to skin cancer. Some XP patients also show clinical characteristics of Cockayne syndrome (CS), a disorder associated with defective preferential repair of DNA lesions in transcriptionally active genes. Cells from the two XP-patients who belong to complementation group D and exhibit additional clinical symptoms of CS are strikingly more sensitive to the cytotoxic effects of UV-light than cells from classical XP-D patients. To explain the severe UV-sensitivity it was suggested that XP-D-CS cells have a defect in preferential repair of UV-induced 6-4 photoproducts (6-4PP) in active genes. We investigated the capacity of XP-D and XP-D-CS cells to repair UV-induced DNA lesions in the active adenosine deaminase gene (ADA) and in the inactive 754 gene by determining (i) the removal of specific lesions, i.e. cyclobutane pyrimidine dimers (CPD) and 6-4PP, or (ii) the formation of BrdUrd-labeled repair patches. No differences in repair capacity were observed between XP-D and XP-D-CS cells. In both cell types repair of CPD was completely absent whereas 6-4PP were inefficiently removed from the ADA gene and the 754 gene with similar kinetics. However, whereas XP-D cells were able to restore UV-inhibited RNA synthesis after a UV-dose of 2 J/m2, RNA synthesis in XP-D-CS cells remained repressed up to 24 h after irradiation. Our results are inconsistent with the hypothesis that differences in the capacity to perform preferential repair of UV-induced photolesions in active genes between XP-D and XP-D-CS cells are the cause of the extreme UV-sensitivity of XP-D-CS cells. Rather, the enhanced sensitivity of XP-D-CS cells may be associated with a defect in transcription regulation superimposed on the repair defect."}

DisGeNET

{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":1003,"end":1022},"obj":"gene:100"},{"id":"T1","span":{"begin":933,"end":935},"obj":"disease:C0043346"},{"id":"T2","span":{"begin":1003,"end":1022},"obj":"gene:100"},{"id":"T3","span":{"begin":942,"end":944},"obj":"disease:C0043346"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"},{"id":"R2","pred":"associated_with","subj":"T2","obj":"T3"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"text":"Cells from XP-D and XP-D-CS patients exhibit equally inefficient repair of UV-induced damage in transcribed genes but different capacity to recover UV-inhibited transcription.\nXeroderma pigmentosum (XP) is a rare hereditary human disorder clinically associated with severe sun sensitivity and predisposition to skin cancer. Some XP patients also show clinical characteristics of Cockayne syndrome (CS), a disorder associated with defective preferential repair of DNA lesions in transcriptionally active genes. Cells from the two XP-patients who belong to complementation group D and exhibit additional clinical symptoms of CS are strikingly more sensitive to the cytotoxic effects of UV-light than cells from classical XP-D patients. To explain the severe UV-sensitivity it was suggested that XP-D-CS cells have a defect in preferential repair of UV-induced 6-4 photoproducts (6-4PP) in active genes. We investigated the capacity of XP-D and XP-D-CS cells to repair UV-induced DNA lesions in the active adenosine deaminase gene (ADA) and in the inactive 754 gene by determining (i) the removal of specific lesions, i.e. cyclobutane pyrimidine dimers (CPD) and 6-4PP, or (ii) the formation of BrdUrd-labeled repair patches. No differences in repair capacity were observed between XP-D and XP-D-CS cells. In both cell types repair of CPD was completely absent whereas 6-4PP were inefficiently removed from the ADA gene and the 754 gene with similar kinetics. However, whereas XP-D cells were able to restore UV-inhibited RNA synthesis after a UV-dose of 2 J/m2, RNA synthesis in XP-D-CS cells remained repressed up to 24 h after irradiation. Our results are inconsistent with the hypothesis that differences in the capacity to perform preferential repair of UV-induced photolesions in active genes between XP-D and XP-D-CS cells are the cause of the extreme UV-sensitivity of XP-D-CS cells. Rather, the enhanced sensitivity of XP-D-CS cells may be associated with a defect in transcription regulation superimposed on the repair defect."}

PubmedHPO

{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":273,"end":288},"obj":"HP_0000992"},{"id":"T2","span":{"begin":311,"end":322},"obj":"HP_0008069"},{"id":"T3","span":{"begin":316,"end":322},"obj":"HP_0002664"}],"text":"Cells from XP-D and XP-D-CS patients exhibit equally inefficient repair of UV-induced damage in transcribed genes but different capacity to recover UV-inhibited transcription.\nXeroderma pigmentosum (XP) is a rare hereditary human disorder clinically associated with severe sun sensitivity and predisposition to skin cancer. Some XP patients also show clinical characteristics of Cockayne syndrome (CS), a disorder associated with defective preferential repair of DNA lesions in transcriptionally active genes. Cells from the two XP-patients who belong to complementation group D and exhibit additional clinical symptoms of CS are strikingly more sensitive to the cytotoxic effects of UV-light than cells from classical XP-D patients. To explain the severe UV-sensitivity it was suggested that XP-D-CS cells have a defect in preferential repair of UV-induced 6-4 photoproducts (6-4PP) in active genes. We investigated the capacity of XP-D and XP-D-CS cells to repair UV-induced DNA lesions in the active adenosine deaminase gene (ADA) and in the inactive 754 gene by determining (i) the removal of specific lesions, i.e. cyclobutane pyrimidine dimers (CPD) and 6-4PP, or (ii) the formation of BrdUrd-labeled repair patches. No differences in repair capacity were observed between XP-D and XP-D-CS cells. In both cell types repair of CPD was completely absent whereas 6-4PP were inefficiently removed from the ADA gene and the 754 gene with similar kinetics. However, whereas XP-D cells were able to restore UV-inhibited RNA synthesis after a UV-dose of 2 J/m2, RNA synthesis in XP-D-CS cells remained repressed up to 24 h after irradiation. Our results are inconsistent with the hypothesis that differences in the capacity to perform preferential repair of UV-induced photolesions in active genes between XP-D and XP-D-CS cells are the cause of the extreme UV-sensitivity of XP-D-CS cells. Rather, the enhanced sensitivity of XP-D-CS cells may be associated with a defect in transcription regulation superimposed on the repair defect."}

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DisGeNET5_gene_disease

DisGeNET

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PubMed:10390531 JSON TXT