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Katja Schneider

Bio: Katja Schneider is an academic researcher from University of Vienna. The author has contributed to research in topics: Homologous recombination & Spo11. The author has co-authored 1 publications.

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TL;DR: In this article, the authors show that MTOPVIB and PRD1 provide the link between the catalytic sub-complex and the other DSB proteins, while PRD3/AtMER2, while localized to the axis, does not assemble a canonical pre-DSB complex but establishes a direct link between DSB-forming and resection machineries.
Abstract: In the current meiotic recombination initiation model, the SPO11 catalytic subunits associate with MTOPVIB to form a Topoisomerase VI-like complex that generates DNA double strand breaks (DSBs). Four additional proteins, PRD1/AtMEI1, PRD2/AtMEI4, PRD3/AtMER2 and the plant specific DFO are required for meiotic DSB formation. Here we show that (i) MTOPVIB and PRD1 provide the link between the catalytic sub-complex and the other DSB proteins, (ii) PRD3/AtMER2, while localized to the axis, does not assemble a canonical pre-DSB complex but establishes a direct link between the DSB-forming and resection machineries, (iii) DFO controls MTOPVIB foci formation and is part of a divergent RMM-like complex including PHS1/AtREC114 and PRD2/AtMEI4 but not PRD3/AtMER2, (iv) PHS1/AtREC114 is absolutely unnecessary for DSB formation despite having a conserved position within the DSB protein network and (v) MTOPVIB and PRD2/AtMEI4 interact directly with chromosome axis proteins to anchor the meiotic DSB machinery to the axis.

19 citations


Cited by
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TL;DR: Crossovers also form a physical link between homologous chromosomes at metaphase I which is critical for accurate chromosome segregation and fertility as mentioned in this paper , and their regulation forms the focus of our current understanding of its regulation.
Abstract: Chromatin state, and dynamic loading of pro-crossover protein HEI10 at recombination intermediates shape meiotic chromosome patterning in plants. Meiosis is the basis of sexual reproduction, and its basic progression is conserved across eukaryote kingdoms. A key feature of meiosis is the formation of crossovers which result in the reciprocal exchange of segments of maternal and paternal chromosomes. This exchange generates chromosomes with new combinations of alleles, increasing the efficiency of both natural and artificial selection. Crossovers also form a physical link between homologous chromosomes at metaphase I which is critical for accurate chromosome segregation and fertility. The patterning of crossovers along the length of chromosomes is a highly regulated process, and our current understanding of its regulation forms the focus of this review. At the global scale, crossover patterning in plants is largely governed by the classically observed phenomena of crossover interference, crossover homeostasis and the obligatory crossover which regulate the total number of crossovers and their relative spacing. The molecular actors behind these phenomena have long remained obscure, but recent studies in plants implicate HEI10 and ZYP1 as key players in their coordination. In addition to these broad forces, a wealth of recent studies has highlighted how genomic and epigenomic features shape crossover formation at both chromosomal and local scales, revealing that crossovers are primarily located in open chromatin associated with gene promoters and terminators with low nucleosome occupancy.

10 citations

Journal ArticleDOI
TL;DR: In this paper , the authors describe a meiotic DSB-defective mutant in barley ( Hordeum vulgare L.), which shows complete sterility due to the absence of meiotic DNA double-strand breaks, synaptonemal complex (SC), and CO formation leading to the occurrence of univalents and their unbalanced segregation into aneuploid gametes.
Abstract: Abstract Key message In barley ( Hordeum vulgare ), MTOPVIB is critical for meiotic DSB and accompanied SC and CO formation while dispensable for meiotic bipolar spindle formation. Abstract Homologous recombination during meiosis assures genetic variation in offspring. Programmed meiotic DNA double-strand breaks (DSBs) are repaired as crossover (CO) or non-crossover (NCO) during meiotic recombination. The meiotic topoisomerase VI (TopoVI) B subunit (MTOPVIB) plays an essential role in meiotic DSB formation critical for CO-recombination. More recently MTOPVIB has been also shown to play a role in meiotic bipolar spindle formation in rice and maize. Here, we describe a meiotic DSB-defective mutant in barley ( Hordeum vulgare L.). CRISPR-associated 9 (Cas9) endonuclease-generated mtopVIB plants show complete sterility due to the absence of meiotic DSB, synaptonemal complex (SC), and CO formation leading to the occurrence of univalents and their unbalanced segregation into aneuploid gametes. In HvmtopVIB plants, we also frequently found the bi-orientation of sister kinetochores in univalents during metaphase I and the precocious separation of sister chromatids during anaphase I. Moreover, the near absence of polyads after meiosis II, suggests that despite being critical for meiotic DSB formation in barley, MTOPVIB seems not to be strictly required for meiotic bipolar spindle formation.

7 citations

Journal ArticleDOI
TL;DR: In this article , the role of the REC114/TOPOVIBL interaction in the formation of double strand break (DSB) in mice was investigated. But the authors did not identify the conserved interacting domains by structural analysis.
Abstract: Meiosis requires the formation of programmed DNA double strand breaks (DSBs), essential for fertility and for generating genetic diversity. DSBs are induced by the catalytic activity of the TOPOVIL complex formed by SPO11 and TOPOVIBL. To ensure genomic integrity, DNA cleavage activity is tightly regulated, and several accessory factors (REC114, MEI4, IHO1, and MEI1) are needed for DSB formation in mice. How and when these proteins act is not understood. Here, we show that REC114 is a direct partner of TOPOVIBL, and identify their conserved interacting domains by structural analysis. We then analyse the role of this interaction by monitoring meiotic DSBs in female and male mice carrying point mutations in TOPOVIBL that decrease or disrupt its binding to REC114. In these mutants, DSB activity is strongly reduced genome-wide in oocytes, and only in sub-telomeric regions in spermatocytes. In addition, in mutant spermatocytes, DSB activity is delayed in autosomes. These results suggest that REC114 is a key member of the TOPOVIL catalytic complex, and that the REC114/TOPOVIBL interaction ensures the efficiency and timing of DSB activity.

6 citations

Journal ArticleDOI
TL;DR: This study provides mechanistic insights into the control of meiotic DSB formation and reveals diverse functional interactions between SPO11-1, PRD3 and the chromosome axis.
Abstract: During meiosis, DNA double-strand breaks (DSBs) occur throughout the genome, a subset of which are repaired to form reciprocal crossovers between chromosomes. Crossovers are essential to ensure balanced chromosome segregation and to create new combinations of genetic variation. Meiotic DSBs are formed by a topoisomerase-VI-like complex, containing catalytic (e.g. SPO11) proteins and auxiliary (e.g. PRD3) proteins. Meiotic DSBs are formed in chromatin loops tethered to a linear chromosome axis, but the interrelationship between DSB-promoting factors and the axis is not fully understood. Here, we study the localisation of SPO11-1 and PRD3 during meiosis, and investigate their respective functions in relation to the chromosome axis. Using immunocytogenetics, we observed that the localisation of SPO11-1 overlaps relatively weakly with the chromosome axis and RAD51, a marker of meiotic DSBs, and that SPO11-1 recruitment to chromatin is genetically independent of the axis. In contrast, PRD3 localisation correlates more strongly with RAD51 and the chromosome axis. This indicates that PRD3 likely forms a functional link between SPO11-1 and the chromosome axis to promote meiotic DSB formation. We also uncovered a new function of SPO11-1 in the nucleation of the synaptonemal complex protein ZYP1. We demonstrate that chromosome co-alignment associated with ZYP1 deposition can occur in the absence of DSBs, and is dependent on SPO11-1, but not PRD3. Lastly, we show that the progression of meiosis is influenced by the presence of aberrant chromosomal connections, but not by the absence of DSBs or synapsis. Altogether, our study provides mechanistic insights into the control of meiotic DSB formation and reveals diverse functional interactions between SPO11-1, PRD3 and the chromosome axis.

5 citations

Journal ArticleDOI
TL;DR: In this paper , the authors show that the ASY1 remodeling complex is temporally and spatially differently assembled and that PCH2 and COMET appear to directly interact in the cytoplasm in early meiosis.
Abstract: Abstract Chromosome axis-associated HORMA domain proteins (HORMADs), e.g. ASY1 in Arabidopsis, are crucial for meiotic recombination. ASY1, as other HORMADs, is assembled on the axis at early meiosis and depleted when homologous chromosomes synapse. Puzzlingly, both processes are catalyzed by AAA+ ATPase PCH2 together with its cofactor COMET. Here, we show that the ASY1 remodeling complex is temporally and spatially differently assembled. While PCH2 and COMET appear to directly interact in the cytoplasm in early meiosis, PCH2 is recruited by the transverse filament protein ZYP1 and brought to the ASY1-bound COMET assuring the timely removal of ASY1 during chromosome synapsis. Since we found that the PCH2 homolog TRIP13 also binds to the ZYP1 homolog SYCP1 in mouse, we postulate that this mechanism is conserved among eukaryotes. Deleting the PCH2 binding site of ZYP1 led to a failure of ASY1 removal. Interestingly, the placement of one obligatory crossover per homologous chromosome pair, compromised by ZYP1 depletion, is largely restored in this separation-of-function zyp1 allele suggesting that crossover assurance is promoted by synapsis. In contrast, this zyp1 allele, similar to the zyp1 null mutant, showed elevated type I crossover numbers indicating that PCH2-mediated eviction of ASY1 from the axis restricts crossover formation.

5 citations