Cell Reports
Volume 14, Issue 11, 22 March 2016, Pages 2519-2527
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Breaks in the 45S rDNA Lead to Recombination-Mediated Loss of Repeats

https://doi.org/10.1016/j.celrep.2016.02.048Get rights and content
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Highlights

  • Human cells are highly sensitive to breaks in 45S, but not 5S, rDNA repeats

  • Homologous recombination inhibits break repair in 45S rDNA

  • SMC5 contributes to recombination-mediated repair of rDNA breaks

  • Recombination-driven repair of 45S rDNA results in loss of repeats and viability

Summary

rDNA repeats constitute the most heavily transcribed region in the human genome. Tumors frequently display elevated levels of recombination in rDNA, indicating that the repeats are a liability to the genomic integrity of a cell. However, little is known about how cells deal with DNA double-stranded breaks in rDNA. Using selective endonucleases, we show that human cells are highly sensitive to breaks in 45S but not the 5S rDNA repeats. We find that homologous recombination inhibits repair of breaks in 45S rDNA, and this results in repeat loss. We identify the structural maintenance of chromosomes protein 5 (SMC5) as contributing to recombination-mediated repair of rDNA breaks. Together, our data demonstrate that SMC5-mediated recombination can lead to error-prone repair of 45S rDNA repeats, resulting in their loss and thereby reducing cellular viability.

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This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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Co-first author

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Present address: European Research Institute for the Biology of Ageing (ERIBA), University Medical Centre Groningen, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, the Netherlands