- DNA Repair Mechanisms
- Nuclear Structure and Function
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Chromosomal and Genetic Variations
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Microtubule and mitosis dynamics
- Mitochondrial Function and Pathology
- Sperm and Testicular Function
- Reproductive Biology and Fertility
- Advanced Electron Microscopy Techniques and Applications
- RNA and protein synthesis mechanisms
- Telomeres, Telomerase, and Senescence
- Skin and Cellular Biology Research
- Animal Genetics and Reproduction
- Protist diversity and phylogeny
- Advanced Fluorescence Microscopy Techniques
- CRISPR and Genetic Engineering
- Molecular Biology Techniques and Applications
- RNA modifications and cancer
- Cellular Mechanics and Interactions
- Nutrition, Genetics, and Disease
- Cell Image Analysis Techniques
- DNA and Nucleic Acid Chemistry
- Epigenetics and DNA Methylation
University of Würzburg
2012-2025
Instituto de Investigaciones Biológicas Clemente Estable
1977-2025
Max Planck Institute for Developmental Biology
2024
Radboud University Nijmegen
2016
University of Tübingen
2016
Leibniz Institute of Plant Genetics and Crop Plant Research
2016
University of Chile
2002
Heidelberg University
1984-2000
German Cancer Research Center
1984-2000
Completion of meiosis in mammals depends on the formation synaptonemal complex, a tripartite structure that physically links homologous chromosomes during prophase I. Several components complex are known, including constituents cohesin core, axial/lateral element and transverse filaments. No protein has previously been identified as an exclusive component central element. Mutations some synaptonemal-complex proteins results impaired meiosis. In humans, cases male infertility have associated...
In mammals, the synaptonemal complex is a structure required to complete crossover recombination. Although suggested by cytological work, in vivo links between structural proteins of and recombination process have not previously been made. The central element traversed DNA at sites presents logical place look for interactions these components. There are four known proteins, three which mutated. Here, we set creating null mutation Syce1 gene mouse. resulting disruption synapsis animals has...
Synapsis is the process by which paired chromosome homologues closely associate in meiosis before crossover. In synaptonemal complex (SC), axial elements of each homologue connect through molecules SYCP1 to central element, contains proteins SYCE1 and -2. We have derived mice lacking SYCE2 protein, producing males females meiotic chromosomes align axes form but do not synapse. Sex are unaligned, forming a sex body. Additionally, markers DNA breakage repair retained on axes, crossover...
The synaptonemal complex (SC) is a proteinaceous, meiosis-specific structure that highly conserved in evolution. During meiosis, the SC mediates synapsis of homologous chromosomes. It essential for proper recombination and segregation chromosomes, therefore genome haploidization. Mutations human genes can cause infertility. In order to gain better understanding process assembly model system would be relevant humans, we are investigating meiosis mice. Here, report on newly identified...
Dynamic repositioning of telomeres is a unique feature meiotic prophase I that highly conserved among eukaryotes. At least in fission yeast it was shown to be required for proper alignment and recombination homologous chromosomes. On entry into meiosis attach the nuclear envelope transiently cluster at limited area form chromosomal bouquet. Telomere clustering thought promote chromosome recognition stable pairing homologs. However, molecular basis telomere attachment movement largely...
Meiotic silencing of sex chromosomes may cause their depletion meiosis-specific genes during evolution. Here, we challenge this hypothesis by reporting the identification TEX11 as first X-encoded factor in mice. forms discrete foci on synapsed regions meiotic and appears to be a novel constituent nodules involved recombination. Loss function causes chromosomal asynapsis reduced crossover formation, leading elimination spermatocytes, respectively, at pachytene anaphase I stages. Specifically,...
The nuclear lamins are major components of a proteinaceous polymer that is located at the interface membrane and chromatin; these solubilized dispersed throughout cytoplasm during mitosis. It has been postulated proteins, assembled into lamina, provide an architectural framework for organization cell nucleus. To test this hypothesis we microinjected lamin antibodies cultured PtK2 cells mitosis, thereby decreasing soluble pool lamins. antibody injected was identified, together with lamins, in...
Background LINC complexes are nuclear envelope bridging protein structures formed by interaction of SUN and KASH proteins. They physically connect the nucleus with peripheral cytoskeleton critically involved in a variety dynamic processes, such as anchorage, movement positioning meiotic chromosome dynamics. Moreover, they shown to be essential for maintaining shape. Findings Based on detailed expression analysis biochemical approaches, we show here that during mouse sperm development,...
Spermatogenesis is a complex differentiation process that involves the successive and simultaneous execution of three different gene expression programs: mitotic proliferation spermatogonia, meiosis, spermiogenesis. Testicular cell heterogeneity has hindered its molecular analyses. Moreover, characterization short, poorly represented stages such as initial meiotic prophase ones (leptotene zygotene) remained elusive, despite their crucial importance for understanding fundamentals meiosis. We...
Significance Synaptonemal complexes (SCs) are meiosis-specific, 200-nm-wide, ladder-like structures that essential for synapsis, recombination, and segregation of homologous chromosomes. Despite its importance the spatial organization individual components during meiosis, molecular architecture SC is still unknown. We used super-resolution imaging by direct stochastic optical reconstruction microscopy ( d STORM), which provides subdiffraction resolution structural investigation SC. The...
Abstract Meiotic recombination generates crossovers between homologous chromosomes that are essential for genome haploidization. The synaptonemal complex is a ‘zipper’-like protein assembly synapses homologue pairs together and provides the structural framework processing sites into crossovers. Humans show individual differences in number of generated across genome. Recently, an anonymous gene variant C14ORF39/SIX6OS1 was identified influences rate humans. Here we encodes component central...
SCP3 is a meiosis-specific structural protein appearing at axial elements and lateral of the synaptonemal complex. We have analysed behaviour cohesin subunit Rad21 in mouse spermatocytes by means squashing technique. Our results demonstrate that both proteins colocalize are partially released from chromosome arms during late prophase I stages, although they persist interchromatid domain metaphase bivalents. Thus, cannot be considered `mitotic'-specific variant, but coexists with Rec8. During...
During the first meiotic prophase, alignment and synapsis of homologous chromosomes are mediated by synaptonemal complex. Incorrect assembly this complex results in cell death, impaired recombination formation aneuploid germ cells. We have identified a novel mouse meiosis-specific protein, TEX12, shown it to be component central element structure at synapsed chromosomes. Only two other proteins, SYCE1 SYCE2, been date and, using several knockout models, we show that these proteins TEX12...
During the extended prophase to meiosis I division, chromosomes assemble axial elements (AE) along replicated sister chromatids whose ends attach inner nuclear membrane (NM) via a specialized conical thickening. Here, we show at EM level that in Sycp3(-/-) spermatocyte lack AE and end thickening, but still they their telomeres NM with an electron-dense plate contains T(2)AG(3) repeats. Immunofluorescence detected telomere proteins, SCP2, meiosis-specific cohesin STAG3 telomere. Bouquet stage...
The synaptonemal complex is an elaborate meiosis-specific supramolecular protein assembly that promotes chromosome synapsis and meiotic recombination. We inactivated the gene Tex12 found TEX12 essential for progression of meiosis in both male female germ cells. Structural analysis Tex12-/- meiocytes revealed a disrupted central element structure, dense structure residing between synapsed homologous chromosomes. Chromosome initiated at multiple positions along paired chromosomes cells, but...
The formation of daughter nuclei and the reformation nucleolar structures was studied after microinjection antibodies to RNA polymerase I into dividing cultured cells (PtK2). fate several proteins representing three main structural subcomponents nucleolus examined by immunofluorescence electron microscopy. results show that do not interfere with normal mitotic progression or early steps nucleologenesis, i.e., aggregation material prenucleolar bodies. However, they inhibit telophasic...
During recent years a number of severe clinical syndromes, collectively termed laminopathies, turned out to be caused by various, distinct mutations in the human LMNA gene. Arising from this, remarkable progress has been made unravel molecular pathophysiology underlying these disorders. A great benefit this context was generation an A-type lamin deficient mouse line (Lmna (-/-) ) Sullivan and others, ( 1) which become one most frequently used models field provided profound insights many...
LINC complexes are evolutionarily conserved nuclear envelope bridges, composed of SUN (Sad-1/UNC-84) and KASH (Klarsicht/ANC-1/Syne/homology) domain proteins. They crucial for positioning shape determination, also mediate (NE) attachment meiotic telomeres, essential driving homolog synapsis recombination. In mice, SUN1 SUN2 the only proteins expressed during meiosis, sharing their localization with meiosis-specific KASH5. Recent studies have shown that loss severely interferes processes....
Synaptonemal complexes (SCs) are evolutionary conserved, meiosis-specific structures that play a central role in synapsis of homologous chromosomes, chiasmata distribution, and chromosome segregation. However, it is still for the most part unclear how SCs do assemble during meiotic prophase. Major components mammalian proteins SCP1, 2, 3. To investigate SCP1 SC assembly, we expressed heterologous system, i.e., COS-7 cells normally not express proteins. Notably, under these experimental...