Mechanisms of Ribosomal DNA Copy-number Regulation
Repetitive DNA sequences are prevalent throughout the genomes of eukaryotes and are risk factors for disease because of their inherent instability. DNA repeats also potentiate evolutionary innovation and buffer against ongoing environmental fluctuation. A major obstacle to studying repetitive DNA is...
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Format: | Dissertation |
Language: | English |
Published: |
ProQuest Dissertations & Theses
01-01-2019
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Online Access: | Get full text |
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Summary: | Repetitive DNA sequences are prevalent throughout the genomes of eukaryotes and are risk factors for disease because of their inherent instability. DNA repeats also potentiate evolutionary innovation and buffer against ongoing environmental fluctuation. A major obstacle to studying repetitive DNA is their inherent masking of each other’s identity, making it difficult to distinguish the contributions of individual repeats and fully investigate the molecular mechanisms that protect DNA arrays from instability. Using an insertion-marker technique to identify individual repeats in the ribosomal DNA array of the budding yeast Saccharomyces cerevisiae, we have uncovered a mechanism for copy number amplification of this essential repetitive DNA sequence. This amplification event occurs through the production of rDNA circles, a previously regarded molecule of disease. Furthermore, the abundance of these DNA circles is responsive to multiple regulatory inputs, including rDNA copy number, rRNA levels, and diet. Together, these data indicate that, in addition to their pathogenic functions, rDNA circles may also serve a positive physiological role. |
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ISBN: | 1392004748 9781392004746 |