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• W2024283562 abstract "Previous work has established that stably transfected human MCF7 cells over-expressing high mobility group A1 proteins (HMGA1) are deficient in global genomic repair (GGR) following exposure to either UV light or cisplatin. To investigate whether HMGA1 over-expression also interferes with gene-specific repair, we employed a rapid and convenient quantitative polymerase chain reaction assay for measuring repair in unique DNA sequences. Efficiency of UV-induced lesion removal was assessed for two genes in MCF7 cells either induced, or not, to over-express transgenic HMGA1 proteins: the constitutively active HPRT gene and the transcriptionally silent β-globin gene. As controls, similar experiments were also performed in non-transgenic MCF7 cells that do not express detectable levels of HMGA1 and in normal human embryonic fibroblasts that naturally over-express HMGA1 proteins. Our results indicate that exposure of cells to a UV dose of 20 J/m2 produced an average of 0.21 ± 0.03 and 0.19 ± 0.02 lesions/kb in the HPRT and β-globin genes, respectively, with no significant difference between HMGA1 over-expressing cells and non-expressing cells. On the other hand, analysis of repair following UV exposure revealed that, compared to controls, HMGA1 over-expressing cells take considerably longer to repair photo-lesions in both the active HPRT and the silent β-globin loci, with non-expressing cells repairing 50% of lesions in HPRT 3–4 h faster than HMGA1 over-expressing cells. Interestingly, the delay in repair is even more prolonged in the silent β-globin locus in HMGA1 over-expressing cells compared to control cells. To our knowledge, this is the first report of HMGA1 proteins inhibiting nucleotide excision repair (NER) within specific genes located in either transcriptionally active “open”, or inactive “closed”, chromatin domains. Furthermore, taken together with previous findings, these results suggest that HMGA1 over-expression interferes with repair processes common to both the GGR and transcription-coupled repair pathways." @default.
• W2024283562 created "2016-06-24" @default.
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• W2024283562 date "2007-09-01" @default.
• W2024283562 modified "2023-09-26" @default.
• W2024283562 title "Gene-specific nucleotide excision repair is impaired in human cells expressing elevated levels of high mobility group A1 nonhistone proteins" @default.
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• W2024283562 doi "https://doi.org/10.1016/j.dnarep.2007.04.003" @default.
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