Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043346 (xeroderma pigmentosum)
 2,924 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Histone acetylation, DNA replicative synthesis, UV-induced DNA repair synthesis, and UV-induced endonuclease-sensitive sites were measured in normal human fibroblasts and xeroderma pigmentosum fibroblasts (complementation groups A, C, and D) following exposure to sodium butyrate. In all four cell types, treatment with millimolar concentrations of sodium butyrate resulted in a hyperacetylation of the core histones. Furthermore, following an exposure of 20 mM sodium butyrate for 48 h, the extent of hyperacetylation was the same in each cell type. In agreement with previous reports, we observed a marked decrease in DNA replicative synthesis in each cell type following increasing times of exposure to sodium butyrate. On the other hand, we observed a marked increase in DNA repair synthesis occurring during early times after UV irradiation in normal cells and in two of the xeroderma pigmentosum cell strains (groups C and D). This increase appeared to correlate with the increase in the highest acetylated form of histone H4. Furthermore, the total number of endonuclease-sensitive sites (i.e. prior to the onset of repair) induced by UV radiation was the same in both butyrated-treated and untreated normal cells over the dose range of 0-20 J/m2. However, the initial rate of removal of these sites increased in butyrate-treated normal cells. These results indicate that sodium butyrate stimulates the initial rate of nucleotide excision repair in both normal and (partially) repair-deficient human cells at concentrations where the histones are maximally hyperacetylated.
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PMID:Sodium butyrate stimulates DNA repair in UV-irradiated normal and xeroderma pigmentosum human fibroblasts. 714 58

Arsenic is an environmental poison and is a grade I human carcinogen that can cause many types of damage to the body. The skin is one of the main target organs of arsenic damage, but the molecular mechanisms underlying arsenic poisoning are not clear. Arsenic is an epigenetic agent. Histone acetylation is one of the earliest covalent modifications to be discovered and is closely related to the occurrence and development of tumors. To investigate the role of acetylated histone H3K18 (H3K18 ac) in arsenic-induced DNA damage, HaCaT cells were exposed to sodium arsenite (NaAsO2) for 24 h. It was found that arsenic induced the downregulation of xeroderma pigmentosum A, D, and F (XPA, XPD, and XPF-nucleotide excision repair (NER)-related genes) expression, as well as histone H3K18 ac expression, and aggravated DNA damage. Chromatin immunoprecipitation quantitative polymerase chain reaction (ChIP-qPCR) analysis showed that H3K18 acetylation in the promoter regions of XPA, XPD, and XPF was downregulated. In addition, the use of the histone deacetylase inhibitor trichostatin A (TSA) partially inhibited arsenic-induced DNA damage, inhibited deacetylation of H3K18 ac in the promoter regions of XPA, XPD, and XPF genes, increased acetylation of H3K18, and promoted the transcriptional expression of NER-related genes. Our study revealed that NaAsO2 induces DNA damage and inhibits the expression of NER-related genes, while TSA increases the H3K18 ac enrichment level and promotes the transcriptional expression of NER, thereby inhibiting DNA damage. These findings provide new ideas for understanding the molecular mechanisms underlying arsenic-induced skin damage.
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PMID:Role of H3K18ac-regulated nucleotide excision repair-related genes in arsenic-induced DNA damage and repair of HaCaT cells. 3203 13