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• W3194020783 abstract "The structure of the human ribosomal DNA (rDNA) cluster has traditionally been hard to analyze owing to its highly repetitive nature. However, the recent development of long-read sequencing technology, such as Oxford Nanopore sequencing, has enabled us to study the large-scale structure of the genome. Using this technology, we found that human cells have a quite regular rDNA structure. Although each human rDNA copy has some variations in its noncoding region, contiguous copies of rDNA are similar, suggesting that homogenization through gene conversion frequently occurs between copies. Analysis of rDNA methylation by Nanopore sequencing further showed that all the noncoding regions are heavily methylated, whereas about half of the coding regions are clearly unmethylated. The ratio of unmethylated copies, which are speculated to be transcriptionally active, was lower in individuals with a higher rDNA copy number, suggesting that there is a mechanism that keeps the active copy number stable. In addition, the rDNA in progeroid syndrome patient cells with reduced DNA repair activity had more unstable copies compared with control normal cells, although the rate was much lower than previously reported using a fiber-FISH method. Collectively, our results clarify the view of rDNA stability and transcription regulation in human cells, indicating the presence of mechanisms for both homogenizations to ensure sequence quality and maintenance of active copies for cellular functions." @default.
• W3194020783 created "2021-08-30" @default.
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• W3194020783 date "2021-08-18" @default.
• W3194020783 modified "2023-10-11" @default.
• W3194020783 title "The human ribosomal DNA array is composed of highly homogenized tandem clusters" @default.
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• W3194020783 doi "https://doi.org/10.1101/gr.275838.121" @default.
• W3194020783 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8559705" @default.
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• W3194020783 hasPublicationYear "2021" @default.
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