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Persistent DNA-break potential near telomeres increases initiation of meiotic recombination on small chromosomes

View ORCID ProfileVijayalakshmi V. Subramanian, Tovah E. Markowitz, View ORCID ProfileLuis A. Vale-Silva, View ORCID ProfilePedro A. San-Segundo, Nancy M. Hollingsworth, View ORCID ProfileAndreas Hochwagen
doi: https://doi.org/10.1101/201889
Vijayalakshmi V. Subramanian
1Department of Biology, New York University, New York, NY 10003, USA
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Tovah E. Markowitz
1Department of Biology, New York University, New York, NY 10003, USA
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Luis A. Vale-Silva
1Department of Biology, New York University, New York, NY 10003, USA
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Pedro A. San-Segundo
2Instituto de Biología Funcional y Genómica, Consejo Superior de Investigaciones Científicas, and University of Salamanca, 37007 Salamanca, Spain
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Nancy M. Hollingsworth
3Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794, USA
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Andreas Hochwagen
1Department of Biology, New York University, New York, NY 10003, USA
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  • For correspondence: andi@nyu.edu
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SUMMARY

Faithful meiotic chromosome inheritance and fertility relies on the stimulation of meiotic crossover recombination by potentially genotoxic DNA double-strand breaks (DSBs). To avoid excessive damage, feedback mechanisms down-regulate DSBs on chromosomes that have successfully initiated crossover repair. In Saccharomyces cerevisiae, this regulation requires the removal of the conserved DSB-promoting protein Hop1/HORMAD during chromosome synapsis. Here, we identify privileged domains spanning roughly 100 Kb near all telomeres that escape this regulation and continue to break in pachynema, well after chromosomes are fully synapsed. These telomere-adjacent regions (TARs) retain Hop1 despite normal synapsis, indicating that synapsis is necessary but not sufficient for Hop1 removal. TAR establishment requires the disassemblase Pch2/TRIP13, which preferentially removes Hop1 from telomere-distant sequences. Importantly, the uniform size of TARs between chromosomes contributes to disproportionately high DSB and repair signals on small chromosomes in pachynema, suggesting that TARs partially underlie the curiously high recombination rate of small chromosomes.

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Posted October 11, 2017.
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Persistent DNA-break potential near telomeres increases initiation of meiotic recombination on small chromosomes
Vijayalakshmi V. Subramanian, Tovah E. Markowitz, Luis A. Vale-Silva, Pedro A. San-Segundo, Nancy M. Hollingsworth, Andreas Hochwagen
bioRxiv 201889; doi: https://doi.org/10.1101/201889
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Persistent DNA-break potential near telomeres increases initiation of meiotic recombination on small chromosomes
Vijayalakshmi V. Subramanian, Tovah E. Markowitz, Luis A. Vale-Silva, Pedro A. San-Segundo, Nancy M. Hollingsworth, Andreas Hochwagen
bioRxiv 201889; doi: https://doi.org/10.1101/201889

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