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

PR domain containing 9 (Prdm9) is 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 b...

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Main Authors: Liu Wang, Barbora Valiskova, Jiri Forejt
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2018-12-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/42511
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author Liu Wang
Barbora Valiskova
Jiri Forejt
author_facet Liu Wang
Barbora Valiskova
Jiri Forejt
author_sort Liu Wang
collection DOAJ
description PR domain containing 9 (Prdm9) is 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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spelling doaj.art-b1c6bf96fb4747848e32560c73f5dc992022-12-22T04:32:28ZengeLife Sciences Publications LtdeLife2050-084X2018-12-01710.7554/eLife.42511Cisplatin-induced DNA double-strand breaks promote meiotic chromosome synapsis in PRDM9-controlled mouse hybrid sterilityLiu Wang0Barbora Valiskova1Jiri Forejt2https://orcid.org/0000-0002-2793-3623BIOCEV Division, Institute of Molecular Genetics, Czech Academy of Sciences, Vestec, Czech RepublicBIOCEV Division, Institute of Molecular Genetics, Czech Academy of Sciences, Vestec, Czech Republic; Faculty of Science, Charles University, Prague, Czech RepublicBIOCEV Division, Institute of Molecular Genetics, Czech Academy of Sciences, Vestec, Czech RepublicPR domain containing 9 (Prdm9) is 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.https://elifesciences.org/articles/42511meiosishybrid sterilityPrdm9DNA double-strand breaks
spellingShingle Liu Wang
Barbora Valiskova
Jiri Forejt
Cisplatin-induced DNA double-strand breaks promote meiotic chromosome synapsis in PRDM9-controlled mouse hybrid sterility
eLife
meiosis
hybrid sterility
Prdm9
DNA double-strand breaks
title Cisplatin-induced DNA double-strand breaks promote meiotic chromosome synapsis in PRDM9-controlled mouse hybrid sterility
title_full Cisplatin-induced DNA double-strand breaks promote meiotic chromosome synapsis in PRDM9-controlled mouse hybrid sterility
title_fullStr Cisplatin-induced DNA double-strand breaks promote meiotic chromosome synapsis in PRDM9-controlled mouse hybrid sterility
title_full_unstemmed Cisplatin-induced DNA double-strand breaks promote meiotic chromosome synapsis in PRDM9-controlled mouse hybrid sterility
title_short Cisplatin-induced DNA double-strand breaks promote meiotic chromosome synapsis in PRDM9-controlled mouse hybrid sterility
title_sort cisplatin induced dna double strand breaks promote meiotic chromosome synapsis in prdm9 controlled mouse hybrid sterility
topic meiosis
hybrid sterility
Prdm9
DNA double-strand breaks
url https://elifesciences.org/articles/42511
work_keys_str_mv AT liuwang cisplatininduceddnadoublestrandbreakspromotemeioticchromosomesynapsisinprdm9controlledmousehybridsterility
AT barboravaliskova cisplatininduceddnadoublestrandbreakspromotemeioticchromosomesynapsisinprdm9controlledmousehybridsterility
AT jiriforejt cisplatininduceddnadoublestrandbreakspromotemeioticchromosomesynapsisinprdm9controlledmousehybridsterility