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Chromosomes are the biologically relevant form of organization of the genome in all known forms of life. Eukaryotes, but not prokaryotes, possess basic proteins, which organize DNA as chromatin, possibly to suppress transcriptional noise and chemical instability and to foster phase separation. Eukaryotes also developed sustainable sexual reproduction, involving regular fusion and fission of genomes, the latter known as meiosis, which converts a diploid precursor cell into four haploid products. In meiosis, homologs from each parent must be identified, linked by chiasmata and finally be transported to opposite meiotic products. We currently address the mechanism of identification, initiated by Spo11 mediated double-strand break formation, as well, as homology search and repair. In most organisms a subset of DSBs is turned into crossing over, the basis of the physical linkage between the homologues. Taken together, we study chromosome segregation mediated by meiotic recombination.
Using budding yeast as model organism, we first established chromosome preparations suitable for immunofluorescence (IF) of yeast chromosomes. Fig. 1 shows spreads representing 10 consecutive stages from premeiotic S-phase until the end of meiosis, 4 haploid nuclei. DNA (blue, DAPI) is decorated with red foci (Smc6 – mediator of genome stability and Holliday-junction resolution) and green lines (Zip1 – mediator of synapsis). For molecular resolution, we perform ChIP-Seq, which yields genome-wide maps of proteins on DNA. For Spo11, we have developed a novel technology, Protec-Seq, which returns meiotic DNA lesions with single nucleotide precision. With this technique, we discovered that dsDNA pieces are excised from chromosomes. Fig. 2 shows such mapped, excised DNA pieces in the form of colored half circles. Of course, we also use the strength of our model system, genetics, to perform forward and reverse genetic screens, and use the ease of genetic manipulations including CRISPR.
1987 Franz Klein received a PhD in yeast genetics with U. Wintersberger (I. Krebsforschung), and moved to D. Schweizer, I. Botanik.
1991 post doc with Breck Byers, U. of Washington.
2000 habilitation in Genetics following the discovery of meiotic cohesin Rec8 and its central role in meiosis.
2008 Coordinator of SFB “Chromosome Dynamics”
2011 full Univ Prof, 2015 Chair of Chromosome Biology.
Dr. Bohr-Gasse 9
1030 Vienna
Room: 5.114
+43-1-4277-56220
Our discovery of COM1/Sae2/CtIP and the defect in DSB repair and synapsis in com1 mutants shows that fully formed, tripartite SC depends on DSB repair (TEM of silver stained yeast spreads). Subsequently orthologs in plants and animals with roles in meiosis and genome stability were discovered. We also found that MRE11 is essential for meiotic DSB repair (Nairz and Klein, 1997; Prinz at all, 1997).
In collaboration with Kim Nasmyth, we discovered scRec8 and demonstrated its fundamental functions. Importantly, the pattern of its localization led us to propose that deposition of cohesin in S-phase is followed by removal of cohesin on chromosome arms to trigger anaphase I (Fig.3 C, D) and removal of cohesin at kinetochores to trigger anaphase II (Fig.3 E, Klein et al., 1999). Now in textbooks.
High resolution mapping of the break machinery revealed its presence at the sites of cohesin, that is, at the chromosome axis (Fig. 4 blue,red symbol). Because DNA breaks occur away from the axis, these sequences must transiently interact with the break machinery for cleavage (Fig.4 red star, Panizza, 2011). DSB formation during axis tethering is likely conserved in all Eukaryotes.
The Smc5/6/Mms21 complex is related to cohesin. We demonstrated that Smc5/6 has 2 independent roles: to prevent and to resolve JMs (Joint Molecules, double Holliday Junctions). Fig.5 shows lethal accumulation of unresolved JMs during synchronous meiosis in smc6-ts (Xaver et al., 2013). Smc5/6 may detect branched DNA molecules to inform helicases (Blooms) or resolvases (Mus81) about their geometry.
We knew for 35 years that meiotic recombination is initiated by chromosome breaks, but only now we discovered that in this process often whole chromosome pieces are chopped out. We developed a novel method to map those fragments, which resulted in unprecedented, single nucleotide accuracy and allowed new key observations, such as to identify a DNA bending motive at preferred cleavage sites.
The mechanism could lead to enhanced chromosome evolution, as well as to pathogenic mutations, if repair fails.
Mustafa Alaabo
+43-1-4277-56221
Room: 5.528/5.530
Doris Chen
PostDoc +43-1-4277-74328
Room: 1.812.3
Theresa Dangl
+43-1-4277-56221
Room: 5.528/5.530
Lisa Kainz
Technician +43-1-4277-56221
Room: 5.528/5.530
Franz Klein
Group Leader +43-1-4277-56220
Room: 5.114
Anna Litwinschuh
+43-1-4277-56221
Room: 5.528/5.530
Viktoria Prast
PhD Student +43-1-4277-56221
Room: 5.528/5.530
Magdalena Vesely
Technician +43-1-4277-56221
Room: 5.528/5.530
Katharina Wieland
Technician +43-1-4277-56221
Room: 5.528/5.530
Spo11 generates gaps through concerted cuts at sites of topological stress.
Prieler, Silvia; Chen, Doris; Huang, Lingzhi; Mayrhofer, Elisa; Zsótér, Soma; Vesely, Magdalena; Mbogning, Jean; Klein, Franz
Transcription dynamically patterns the meiotic chromosome-axis interface.
Sun, Xiaoji; Huang, Lingzhi; Markowitz, Tovah E; Blitzblau, Hannah G; Chen, Doris; Klein, Franz; Hochwagen, Andreas
Smc5/6-Mms21 prevents and eliminates inappropriate recombination intermediates in meiosis.
Martin Xaver, Lingzhi Huang, Doris Chen and Franz Klein
Spo11-accessory proteins link double-strand break sites to the chromosome axis in early meiotic recombination.
Panizza, Silvia; Mendoza, Marco A; Berlinger, Marc; Huang, Lingzhi; Nicolas, Alain; Shirahige, Katsuhiko; Klein, Franz
Franz Klein is speaker of the Special Research Area (SFB) "Chromosome Dynamics - Unraveling the function of chromosomal domains" funded by the Austrian Science Fund FWF. SFB's are peer-reviewed, highly interactive research networks, established to foster long-term, interdisciplinary co-operation of local research groups working on the frontiers of their thematic areas.
The Group Klein participates in in the special Doctoral Program 'Chromosome Dynamics' reviewed and funded by the Austrian Research Fund FWF.
Identifying and exploiting cell-state dependent metabolic programs
11:00 - 12:00
IMP Lecture HallChromatin as a gatekeeper of chromosome replication
11:30 - 12:30 Max Perutz Labs SR 1 (6th floor)Mind matters. VBC mental health awareness
13:30 - 14:30 IMP Lecture HallThe multiple facets of Hop1 during meiotic prophase
11:30 - 12:30 Max Perutz Labs SR 1 (6th floor)Chromosomes as Mechanical Objects: from E.coli to Meiosis to Mammalian cells
11:00 - 12:00 IMBA/GMI Lecture HallConvergent evolution of CO2-fixing liquid-liquid phase separation
11:30 - 12:30 GMI Orange Seminar RoomViral envelope engineering for cell type specific delivery
16:00 - 17:00 IMP Seminar Room 1.014/16New ways of leading: inclusive leadership and revising academic hierarchies
14:15 - 15:15 IMP Lecture HallHow an opportunistic human pathogen colonizes surfaces - From pathogen behavior to new drugs
13:15 - 14:15 UBB - Lecture Hall 1Title to be announced
14:00 - 15:00 Lecture Hall AandB, VBC5Decoding Molecular Plasticity in the Dark Proteome of the Nuclear Pore Complex
11:00 - 12:00 IMBA/GMI Lecture HallProbing the 3D genome architectural basis of neurodevelopment and aging in vivo
17:00 - 18:00 ZoomHow to tango with four - the evolution of meiotic chromosome segregation after genome duplication
11:30 - 12:30 Max Perutz Labs SR 1 (6th floor)Multidimensional approach to decoding the mysteries of animal development
13:15 - 14:15 UBB - Lecture Hall 1Membrane remodeling proteins at the junction between prokaryotes and eukaryotes
13:15 - 14:15 UBB - Lecture Hall 1Connecting mitotic chromosomes to dynamic microtubules - insight from biochemical reconstitution
11:30 - 12:30 Max Perutz Labs SR 1 (6th floor)Neurodiversity in academia: strengths and challenges of neurodivergence
14:00 - 15:00 IMP Seminar Room 1.014/16Gene expression dynamics during the awakening of the zygotic genome
11:00 - 12:00 IMBA/GMI Lecture HallWhen all is lost? Measuring historical signals
13:15 - 14:15 UBB - Lecture Hall 1Suckers and segments of the octopus arm
11:00 - 12:00 IMBA/GMI Lecture HallUsing the house mouse radiation to study the rapid evolution of genes and genetic processes
13:15 - 14:15 UBB - Lecture Hall 1CRISPR jumps ahead: mechanistic insights into CRISPR-associated transposons
11:30 - 12:30 Max Perutz Labs SR 1 (6th floor)Title to be announced
11:30 - 12:30 Max Perutz Labs SR 1 (6th floor)Enigmatic evolutionary origin and multipotency of the neural crest cells - major drivers of vertebrate evolution
13:15 - 14:15 UBB - Lecture Hall 1Visualising mitotic chromosomes and nuclear dynamics by correlative light and electron microscopy
11:30 - 12:30 Max Perutz Labs SR 1 (6th floor)Bacterial cell envelope homeostasis at the (post)transcriptional level
13:15 - 14:15 UBB - Lecture Hall 1Polyploidy and rediploidisation in stressful times
13:15 - 14:15 UBB - Lecture Hall 1Prdm9 control of meiotic synapsis of homologs in intersubspecific hybrids
11:30 - 12:30 Max Perutz Labs SR 1 (6th floor)RNA virus from museum specimens
13:15 - 14:15 UBB - Lecture Hall 1Programmed DNA double-strand breaks during meiosis: Mechanism and evolution
11:30 - 12:30 Max Perutz Labs SR 1 (6th floor)Title to be announced
11:00 - 12:00
