Cisplatin-induced DNA double-strand breaks promote meiotic chromosome synapsis in PRDM9-controlled mouse hybrid sterility

  1. Liu Wang
  2. Barbora Valiskova
  3. Jiri Forejt  Is a corresponding author
  1. Academy of Sciences of the Czech Republic, Czech Republic

Abstract

PR domain containing 9 (Prdm9) is a gene specifying hotspots of meiotic recombination but in hybrids between two mouse subspecies Prdm9 controls failure of meiotic chromosome synapsis and hybrid male sterility. We have previously reported that Prdm9-controlled asynapsis and meiotic arrest are conditioned by the inter-subspecific heterozygosity of the hybrid genome and we presumed that the insufficient number of properly repaired PRDM9-dependent DNA double-strand breaks (DSBs) causes asynapsis of chromosomes and meiotic arrest (Gregorova et al. 2018). We now extend the evidence for the lack of properly processed DSBs by improving meiotic chromosome synapsis with exogenous DSBs. A single injection of chemotherapeutic drug cisplatin increased frequency of RPA and DMC1 foci at the zygotene stage of sterile hybrids, enhanced homolog recognition and increased the proportion of spermatocytes with fully synapsed homologs at pachytene. The results bring a new evidence for a DSB-dependent mechanism of synapsis failure and infertility of intersubspecific hybrids.

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All data generated or analyzed during this study are included in the manuscript and source files

Article and author information

Author details

  1. Liu Wang

    Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vestec, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  2. Barbora Valiskova

    Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vestec, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  3. Jiri Forejt

    Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vestec, Czech Republic
    For correspondence
    jforejt@img.cas.cz
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2793-3623

Funding

Grantova Agentura Ceske Republiky (16-01969S)

  • Jiri Forejt

Ministry of Education Youth and Sports of the Czech Republic (LQ1604 project of NSPII)

  • Jiri Forejt

Charles University Grant Agency of the Czech Republic (17115)

  • Barbora Valiskova

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: The project was approved by the Animal Care and Use Committee of the Institute of Molecular Genetics AS CR, protocol No 141/2012. The principles of laboratory animal care, Czech Act No. 246/1992 Sb., compatible with EU Council Directive 86/609/EEC and Appendix of the Council of Europe Convention ETS, were observed.

Reviewing Editor

  1. Patricia J Wittkopp, University of Michigan, United States

Version history

  1. Received: October 3, 2018
  2. Accepted: December 27, 2018
  3. Accepted Manuscript published: December 28, 2018 (version 1)
  4. Version of Record published: January 8, 2019 (version 2)

Copyright

© 2018, Wang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Liu Wang
  2. Barbora Valiskova
  3. Jiri Forejt
(2018)
Cisplatin-induced DNA double-strand breaks promote meiotic chromosome synapsis in PRDM9-controlled mouse hybrid sterility
eLife 7:e42511.
https://doi.org/10.7554/eLife.42511

Share this article

https://doi.org/10.7554/eLife.42511

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