scholarly journals Modulation of Prdm9-controlled meiotic chromosome asynapsis overrides hybrid sterility in mice

2017 ◽  
Author(s):  
Sona Gregorova ◽  
Vaclav Gergelits ◽  
Irena Chvatalova ◽  
Tanmoy Bhattacharyya ◽  
Barbora Valiskova ◽  
...  
Keyword(s):  
Meiotic Chromosome ◽  
Hybrid Sterility ◽  
Mouse Strains ◽  
Dna Double Strand Breaks ◽  
Closely Related Species ◽  
Strand Breaks ◽  
Homologous Chromosomes ◽  
Recombination Hotspots ◽  
Chromosome Synapsis ◽  
Reproductive Isolation Mechanisms

AbstractThe infertility of hybrids between closely related species is one of the reproductive isolation mechanisms leading to speciation. Prdm9, the only known vertebrate hybrid sterility gene causes failure of meiotic chromosome synapsis and infertility in male hybrids between mouse strains derived from two mouse subspecies. Within species Prdm9 determines the sites of programmed DNA double-strand breaks and meiotic recombination hotspots. To investigate the relation between Prdm9-controlled meiotic arrest and asynapsis, we inserted random stretches of consubspecific homology on several autosomal pairs in sterile hybrids and analyzed their ability to form synaptonemal complexes and rescue male fertility. Twenty-seven or more Mb of consubspecific homology fully restored synapsis in a given autosomal pair and we predicted that two symmetric DSBs or more per chromosome are necessary for successful meiosis. We hypothesize that impaired recombination between evolutionary diverged homologous chromosomes could function as one of the mechanisms of hybrid sterility occurring in various sexually reproducing species.

scholarly journals Modulation of Prdm9-controlled meiotic chromosome asynapsis overrides hybrid sterility in mice

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Sona Gregorova ◽  
Vaclav Gergelits ◽  
Irena Chvatalova ◽  
Tanmoy Bhattacharyya ◽  
Barbora Valiskova ◽  
...  
Keyword(s):  
Meiotic Chromosome ◽  
Hybrid Sterility ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Recombination Hotspots ◽  
Chromosome Synapsis ◽  
Reproductive Isolation Mechanisms ◽  
Meiotic Recombination Hotspots ◽  
Isolation Mechanisms

Hybrid sterility is one of the reproductive isolation mechanisms leading to speciation. Prdm9, the only known vertebrate hybrid-sterility gene, causes failure of meiotic chromosome synapsis and infertility in male hybrids that are the offspring of two mouse subspecies. Within species, Prdm9 determines the sites of programmed DNA double-strand breaks (DSBs) and meiotic recombination hotspots. To investigate the relation between Prdm9-controlled meiotic arrest and asynapsis, we inserted random stretches of consubspecific homology on several autosomal pairs in sterile hybrids, and analyzed their ability to form synaptonemal complexes and to rescue male fertility. Twenty-seven or more megabases of consubspecific (belonging to the same subspecies) homology fully restored synapsis in a given autosomal pair, and we predicted that two or more DSBs within symmetric hotspots per chromosome are necessary for successful meiosis. We hypothesize that impaired recombination between evolutionarily diverged chromosomes could function as one of the mechanisms of hybrid sterility occurring in various sexually reproducing species.

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

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Liu Wang ◽  
Barbora Valiskova ◽  
Jiri Forejt
Keyword(s):  
Meiotic Chromosome ◽  
Hybrid Sterility ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Hybrid Male ◽  
Meiotic Arrest ◽  
Strand Breaks ◽  
Chromosome Synapsis ◽  
Hybrid Genome ◽  
Pr Domain

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 (<xref ref-type="bibr" rid="bib18">Gregorova et al., 2018</xref>). 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.

scholarly journals ANKRD31 regulates spatiotemporal patterning of meiotic recombination initiation and ensures recombination between heterologous sex chromosomes in mice

2018 ◽  
Author(s):  
Frantzeskos Papanikos ◽  
Julie A.J. Clément ◽  
Erika Testa ◽  
Ramya Ravindranathan ◽  
Corinne Grey ◽  
...  
Keyword(s):  
Sex Chromosomes ◽  
Meiotic Recombination ◽  
Meiotic Chromosome ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Homologous Chromosomes ◽  
Y Chromosomes ◽  
Genome Wide ◽  
A Genome ◽  
Pseudoautosomal Regions

AbstractOrderly segregation of chromosomes during meiosis requires that crossovers form between homologous chromosomes by recombination. Programmed DNA double-strand breaks (DSBs) initiate meiotic recombination. We identify ANKRD31 as a critical component of complexes of DSB-promoting proteins which assemble on meiotic chromosome axes. Genome-wide, ANKRD31 deficiency causes delayed recombination initiation. In addition, loss of ANKRD31 alters DSB distribution owing to reduced selectivity for sites that normally attract DSBs. Strikingly, ANKRD31 deficiency also abolishes uniquely high rates of recombination that normally characterize pseudoautosomal regions (PARs) of X and Y chromosomes. Consequently, sex chromosomes do not form crossovers leading to chromosome segregation failure in ANKRD31-deficient spermatocytes. These defects are accompanied by a genome-wide delay in assembling DSB-promoting proteins on axes and a loss of a specialized PAR-axis domain that is highly enriched for DSB-promoting proteins. Thus, we propose a model for spatiotemporal patterning of recombination by ANKRD31-dependent control of axis-associated complexes of DSB-promoting proteins.

scholarly journals Three Distinct Modes of Mec1/ATR and Tel1/ATM Activation Illustrate Differential Checkpoint Targeting during Budding Yeast Early Meiosis

2013 ◽  
Vol 33 (16) ◽  
pp. 3365-3376 ◽  
Author(s):  
Yun-Hsin Cheng ◽  
Chi-Ning Chuang ◽  
Hui-Ju Shen ◽  
Feng-Ming Lin ◽  
Ting-Fang Wang
Keyword(s):  
Dna Replication ◽  
Budding Yeast ◽  
Noncovalent Interactions ◽  
Double Strand Breaks ◽  
Histone H2a ◽  
Dna Double Strand Breaks ◽  
Dsb Repair ◽  
Strand Breaks ◽  
Homologous Chromosomes ◽  
Chromosome Synapsis

Recombination and synapsis of homologous chromosomes are hallmarks of meiosis in many organisms. Meiotic recombination is initiated by Spo11-induced DNA double-strand breaks (DSBs), whereas chromosome synapsis is mediated by a tripartite structure named the synaptonemal complex (SC). Previously, we proposed that budding yeast SC is assembled via noncovalent interactions between the axial SC protein Red1, SUMO chains or conjugates, and the central SC protein Zip1. Incomplete synapsis and unrepaired DNA are monitored by Mec1/Tel1-dependent checkpoint responses that prevent exit from the pachytene stage. Here, our results distinguished three distinct modes of Mec1/Tec1 activation during early meiosis that led to phosphorylation of three targets, histone H2A at S129 (γH2A), Hop1, and Zip1, which are involved, respectively, in DNA replication, the interhomolog recombination and chromosome synapsis checkpoint, and destabilization of homology-independent centromere pairing. γH2A phosphorylation is Red1 independent and occurs prior to Spo11-induced DSBs. DSB- and Red1-dependent Hop1 phosphorylation is activated via interaction of the Red1-SUMO chain/conjugate ensemble with the Ddc1-Rad17-Mec3 (9-1-1) checkpoint complex and the Mre11-Rad50-Xrs2 complex. During SC assembly, Zip1 outcompetes 9-1-1 from the Red1-SUMO chain ensemble to attenuate Hop1 phosphorylation. In contrast, chromosome synapsis cannot attenuate DSB-dependent and Red1-independent Zip1 phosphorylation. These results reveal how DNA replication, DSB repair, and chromosome synapsis are differentially monitored by the meiotic checkpoint network.

scholarly journals De novo deletion mutations at recombination hotspots in mouse germlines

2020 ◽  
Author(s):  
Agnieszka Lukaszewicz ◽  
Julian Lange ◽  
Scott Keeney ◽  
Maria Jasin
Keyword(s):  
De Novo ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Atm Kinase ◽  
Strand Breaks ◽  
Homologous Chromosomes ◽  
Recombination Hotspots ◽  
Genome Wide ◽  
Meiotic Dsbs ◽  
Meiotic Recombination Hotspots

AbstractNumerous DNA double-strand breaks (DSBs) arise genome-wide during meiosis to ensure recombination between homologous chromosomes, which is required for gamete formation1,2. The ATM kinase plays a central role in controlling both the number and position of DSBs3-5, but the consequences of deregulated DSB formation have not been explored. Here we discovered that an unanticipated type of DNA deletion arises at meiotic recombination hotspots in the absence of ATM. Deletions form via joining of ends from two closely-spaced DSBs at adjacent hotspots or within a single hotspot. Deletions are also detected in normal cells, albeit at much lower frequency, revealing that the meiotic genome has a hidden potential for deletion events. Remarkably, a subset of deletions contain insertions that likely originated from DNA fragments released from hotspots on other chromosomes. Moreover, although deletions form primarily within one chromosome, joining between homologous chromosomes is also observed. This predicts in turn gross chromosome rearrangements, with evidence of damage to multiple chromatids and aborted gap repair. Thus, multiple nearby meiotic DSBs are normally suppressed by ATM to protect genomic integrity. We expect the de novo germline mutations we observe to affect human health and genome evolution.

scholarly journals Impeding DNA Break Repair Enables Oocyte Quality Control

2018 ◽  
Author(s):  
Huanyu Qiao ◽  
H.B.D. Prasada Rao ◽  
Yan Yun ◽  
Sumit Sandhu ◽  
Jared H. Fong ◽  
...  
Keyword(s):  
Quality Control ◽  
Oocyte Quality ◽  
Double Strand Breaks ◽  
Negative Regulator ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Homologous Chromosomes ◽  
Chromosome Synapsis ◽  
Sumo Ligase ◽  
Induced Apoptosis

SUMMARYOocyte quality control culls eggs with defects in meiosis. In mouse, oocyte death is triggered by defects in chromosome synapsis and recombination, which involve repair of programmed DNA double-strand breaks (DSBs) between homologous chromosomes. We show that RNF212, a SUMO ligase required for crossing over, also mediates oocyte quality control. Both physiological apoptosis and wholesale oocytes elimination in meiotic mutants require RNF212. RNF212 sensitizes cells to DSB-induced apoptosis within a narrow window when chromosomes desynapse during the transition into quiescence. Analysis of DNA damage during this transition implies that RNF212 impedes DSB repair. Consistently, RNF212 is required for HORMAD1, a negative regulator of inter-sister recombination, to associate with desynapsing chromosomes. We infer that oocytes impede repair of residual DSBs to retain a “memory” of meiotic defects that enables quality control processes. These results define the logic of oocyte quality control and suggest RNF212 variants may influence transmission of defective genomes.

scholarly journals Reproductive Isolation Between Taxonomically Controversial Forms of the Gray Voles (Microtus, Rodentia; Arvicolinae): Cytological Mechanisms and Taxonomical Implications

2021 ◽  
Vol 12 ◽  
Author(s):  
Tatiana I. Bikchurina ◽  
Fedor N. Golenishchev ◽  
Elena A. Kizilova ◽  
Ahmad Mahmoudi ◽  
Pavel M. Borodin
Keyword(s):  
Hybrid Sterility ◽  
Taxonomic Status ◽  
Double Strand Breaks ◽  
Valid Species ◽  
F1 Hybrids ◽  
Phylogenetic Distance ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Chromosome Synapsis ◽  
Male Hybrid

The formation of hybrid sterility is an important stage of speciation. The voles of the genus Microtus, which is the most speciose genus of rodents, provide a good model for studying the cytological mechanisms of hybrid sterility. The voles of the “mystacinus” group of the subgenus Microtus (2n = 54) comprising several recently diverged forms with unclear taxonomic status are especially interesting. To resolve the taxonomic status of Microtus mystacinus and Microtus kermanensis, we crossed both with Microtus rossiaemeridionalis, and M. kermanensis alone with Microtus arvalis “obscurus” and M. transcaspicus and examined the reproductive performance of their F1 hybrids. All interspecies male hybrids were sterile. Female M. kermanensis × M. arvalis and M. kermanensis × M. transcaspicus hybrids were sterile as well. Therefore, M. mystacinus, M. kermanensis, and M. rossiaemeridionalis could be considered valid species. To gain an insight into the cytological mechanisms of male hybrid sterility, we carried out a histological analysis of spermatogenesis and a cytological analysis of chromosome synapsis, recombination, and epigenetic chromatin modifications in the germ cells of the hybrids using immunolocalization of key meiotic proteins. The hybrids showed wide variation in the onset of spermatogenesis arrest stage, from mature (although abnormal) spermatozoa to spermatogonia only. Chromosome asynapsis was apparently the main cause of meiotic arrest. The degree of asynapsis varied widely across cells, individuals, and the crosses—from partial asynapsis of several small bivalents to complete asynapsis of all chromosomes. The asynapsis was accompanied by a delayed repair of DNA double-strand breaks marked by RAD51 antibodies and silencing of unpaired chromatin marked by γH2A.X antibodies. Overall, the severity of disturbances in spermatogenesis in general and in chromosome synapsis in particular increased in the hybrids with an increase in the phylogenetic distance between their parental species.

Sign in / Sign up

Export Citation Format

Share Document