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Genomic copy-number loss is rescued by self-limiting production of DNA circles

Andrés Mansisidor, Temistocles Molinar Jr., Priyanka Srivastava, Hannah Blitzblau, Hannah Klein, Andreas Hochwagen
doi: https://doi.org/10.1101/255471
Andrés Mansisidor
Department of Biology, New York University, New York, NY 10003
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Temistocles Molinar
Department of Biology, New York University, New York, NY 10003
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Priyanka Srivastava
Department of Biology, New York University, New York, NY 10003
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Hannah Blitzblau
Biology Department, Massachusetts Institute of Technology, Cambridge, MA 02139
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Hannah Klein
Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016
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Andreas Hochwagen
Department of Biology, New York University, New York, NY 10003
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  • For correspondence: andi@nyu.edu
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Summary

Copy-number changes generate phenotypic variability in health and disease. Whether organisms protect against copy-number changes is largely unknown. Here, we show that Saccharomyces cerevisiae monitors the copy number of its ribosomal DNA (rDNA) and rapidly responds to copy-number loss with the clonal amplification of extrachromosomal rDNA circles (ERCs) from chromosomal repeats. ERC production is proportional to repeat loss and reaches a dynamic steady state that responds to the addition of exogenous rDNA copies. ERC levels are also modulated by RNAPI activity and diet, suggesting that rDNA copy number is calibrated against the cellular demand for rRNA. Lastly, we show that ERCs reinsert into the genome in a dosage-dependent manner, indicating that they provide a reservoir for ultimately increasing rDNA array length. Our results reveal a DNA-based mechanism for rapidly restoring copy number in response to catastrophic gene loss that shares fundamental features with unscheduled copy-number amplifications in cancer cells.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted January 29, 2018.
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Genomic copy-number loss is rescued by self-limiting production of DNA circles
Andrés Mansisidor, Temistocles Molinar Jr., Priyanka Srivastava, Hannah Blitzblau, Hannah Klein, Andreas Hochwagen
bioRxiv 255471; doi: https://doi.org/10.1101/255471
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Genomic copy-number loss is rescued by self-limiting production of DNA circles
Andrés Mansisidor, Temistocles Molinar Jr., Priyanka Srivastava, Hannah Blitzblau, Hannah Klein, Andreas Hochwagen
bioRxiv 255471; doi: https://doi.org/10.1101/255471

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