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In each generation, the two parental genomes must pair, recombine, and segregate to a newly mixed set of haploid chromosomes in a specialized cell division called meiosis. Failures in this process lead to miscarriages and congenital diseases. Research in my lab is directed towards the identification of genes and processes essential for accurate chromosome segregation during meiosis. For this, we study the meiotic entry network, which ensures the timely coordination and initiation of meiotic processes. We study the mechanisms of recognition and the well-ordered side-by-side alignment of homologous chromosomes. Furthermore, we are interested in the roles of topoisomerases during meiotic recombination, and their function in resolving unwanted chromosomal connections or crossover intermediates. The identification of any new risk factor leading to unfaithful partitioning of chromosomes into gametes is of high relevance to human health.
Excellent forward and reverse genetics, easy cytological observation of all meiotic stages and the transparency of the animal make the nematode Caenorhabditis elegans an excellent model system for our studies. State-of-the art CRISPR/Cas technologies are well established and allow the rapid generation of novel alleles and tagging of individual factors that can be followed by high-resolution imaging. This way we have generated numerous novel meiotic mutants that provide(d) us insight into events of prophase I of meiosis.
Verena Jantsch-Plunger studied Biochemistry at the University of Vienna. She conducted her diploma and PhD work at the Carnegie Institution of Washington under the supervision of Nobel Laureate Dr. Andrew Fire (discovery of RNA-interference). She earned her PhD in 1993 at the University of Vienna. Since 2017 she is Prof. of Eukaryote Genetics at the University of Vienna.
My lab gained crucial insights into meiotic chromosome movement. In Caenorhabditis elegans abrogation of movement leads to the establishment of the synaptonemal complex between non-homologous DNA sequences. We found that SUN-1 is part of a complex that transduces mechanical forces and signals across the nuclear membrane and connects chromosomes in the nucleus to the force generating cytoplasmic apparatus. The complex ensures chromosome movement until essential meiotic tasks required to build a crossover have been fullfilled.
DOI: 10.1016/j.devcel.2007.05.004
DOI: 10.1016/j.cell.2009.10.045
DOI: 10.1371/journal.pgen.1001219
DOI: 10.1371/journal.pgen.1003335
DOI: 10.1007/s00412-013-0436-7
DOI: 10.1016/j.cub.2016.09.007
DOI: 10.1016/j.devcel.2018.03.018
We show how lamins “increase the fluidity of the nuclear membrane” during chromosome movement in the earliest stage of prophase I. By artificially increasing the rigidity of the lamina, we could demonstrate reduced chromosome movement resulting in abnormal chromosomes and increased apoptosis. We deciphered that cross talk between the lamina opening and events at the chromosomes exists.
DOI: 10.1016/j.devcel.2018.03.018
We demonstrated that the C. elegans homolog of a conserved DNA repair factor RMI1 (RecQ-mediated genome instability protein 1) plays multiple genetically separable roles that together ensure the faithful inheritance of intact genomes during sexual reproduction. Strikingly, it spatially regulates the distribution of crossovers on chromosomes, demonstrating that the RTR (RecQ helicase-topoisomerase-RMI1/2) complex can act locally within specific chromosome domains.
DOI: 10.1371/journal.pbio.1002412
Transient and Partial Nuclear Lamina Disruption Promotes Chromosome Movement in Early Meiotic Prophase.
Link Jana, Paouneskou Dimitra, Velkova Maria, Daryabeigi Anahita, Laos Triin, Labella Sara, Barroso Consuelo, Pacheco Piñol Sarai, Montoya Alex, Kramer Holger, Woglar Alexander, Baudrimont Antoine, Markert Sebastian Mathias, Stigloher Christian, Martinez-Perez Enrique, Dammermann Alexander, Alsheimer Manfred, Zetka Monique, Jantsch Verena
Matefin/SUN-1 phosphorylation is part of a surveillance mechanism to coordinate chromosome synapsis and recombination with meiotic progression and chromosome movement.
Woglar Alexander, Daryabeigi Anahita, Adamo Adele, Habacher Cornelia, Machacek Thomas, La Volpe Adriana, Jantsch Verena
Meiotic chromosome homology search involves modifications of the nuclear envelope protein Matefin/SUN-1.
Penkner Alexandra M, Fridkin Alexandra, Gloggnitzer Jiradet, Baudrimont Antoine, Machacek Thomas, Woglar Alexander, Csaszar Edina, Pasierbek Pawel, Ammerer Gustav, Gruenbaum Yosef, Jantsch Verena
The Group Jantsch participates in in the special Doctoral Program 'Chromosome Dynamics' reviewed and funded by the Austrian Research Fund FWF.