Genetic information in humans is encoded in 23 chromosome pairs, where one pair consists of two slightly different copies or homologs. One is inherited from the father and one from the mother. Human gametes, however, are haploid - they start out with only half the number of chromosomes. When gametes fuse during sexual reproduction they create an organism with the full set of chromosomes. The random assortment of parental chromosomes together with the exchange of genetic material between homologous chromosomes during early meiosis, account for genetic diversity in the offspring.
Meiosis begins with controlled self-harm
Each human gamete contains one of billions of possible combinations of the genetic information they inherit from their parental cells. Sexually reproducing organisms take a high risk to achieve this diversity. To initiate meiotic recombination, cells introduce hundreds of dangerous DNA DSBs in chromosomes with an enzyme called Spo11-complex. By using the homologous copy as a template, the breaks are repaired and genetic information is exchanged between chromosomes. “Cells have been observed to keep double strand breaks far apart from one another”, explains group leader Franz Klein. “However, rather surprisingly, we have now discovered that approximately 20% of breaks correspond to closely positioned pairs of DSBs, that punch out entire pieces of the chromosome. These gaps can also initiate recombination, something that has not been considered before.”
Spo11 recognizes physical strain of DNA
The team led by molecular biologist Dr. Silvia Prieler and bioinformatician Dr. Doris Chen mapped the liberated fragments across the entire yeast genome with single nucleotide precision, better than DSBs had ever been mapped before. This precision led to several new observations, for instance that DNA may have to be bent during the cleavage reaction. They also found that sites where DNA is frequently under high topological stress are cleaved more efficiently. During transcription, the two DNA strands are separated to allow RNA production. This causes the DNA-strands on both sides of the transcription-bubble to be over- or underwound and generates considerable physical strain. This kind of topological strain is resolved by so-called topoisomerases, to which the Spo11-complex is closely related. A key question, therefore, is why a topoisomerase-relative initiates meiotic recombination, given that the cell has dedicated nucleases that could cleave the DNA. “The goal in meiosis is to provide chances for novel genetic combination on as many sites as possible, to combine even closely spaced parental alleles”, says Franz Klein. “Our study provides a hint as to why Spo11 may be so suitable to initiate meiotic recombination: instead of recognizing specific DNA sequences, which would recombine chromosomes always at predetermined positions, it recognizes stressed DNA, something that can occur at any sequence that is frequently used.”
High risk – high potential
Why cells undergo the risk to punch out chromosome pieces is still unclear. The gaps and their corresponding fragments pose an enhanced risk for mutations, caused by deletions or by the insertion of fragments in irregular positions. The scientists show that although these pairs of double strand breaks are spread across the genome, they often correspond with promoter regions that are especially prone to topological stress. Promoters are genetic elements that regulate the level of transcription. “Evolutionarily, it would be great to be able to exchange functional regulatory elements between different sites in the genome. This raises the intriguing possibility that meiotic gaps at double DSBs could stimulate the evolution of control elements in the genome”, concludes Franz Klein. A risky business for a single cell, no doubt, but perhaps worth the risk for the species.
Publication:
Silvia Prieler, Doris Chen, Lingzhi Huang, Elisa Mayrhofer, Soma Zsótér, Magdalena, Vesely, Jean Mbogning, Franz Klein: Spo11 generates chromosomal gaps through 1 concerted cuts at sites of topological stress. Nature 2021
Screening for RNA-peptide interactions using high-density peptide arrays
Speaker: Alexander Nesterov-MuellerInstitute: KIT Karlsruhe Institute of TechnologyHost: Bojan Zagrovic
Monday Seminar (Internal)
Speaker: BUSETTO Virginia (Falk), HARVEY Zachary (Berger), MILOJKOVIC Lidija (Urban)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Sensory coding to memory formation: a functional and evolutionary perspective
Speaker: Simon SprecherInstitute: University of FribourgHost: Oleg Simakov
m5C-modifications of ribosomal RNA modulate healthy lifespan and development
Speaker: Markus SchossererInstitute: Medical University ViennaHost: Christopher Campbell
Endolysosomal biogenesis - from Rab activation to membrane fusion
Speaker: Christian UngermannInstitute: University of OsnabrückHost: Gang Dong
Structural Insights into the light-harvesting antenna and photoprotection mechanism in cyanobacteria
Speaker: Tina Dominguez-MartinInstitute: University of CordobaHost: Silvia Ramundo
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Speaker: PANAROTTO-PERICLES Melanie (Peters), KOLESNIKOVA Sofia (Gerlich), HANDLER Dominik (Brennecke)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Elucidation of plant growth-regulatory networks through multiplex gene editing
Speaker: Dirk InzeInstitute: VIBHost: Andreas Bachmair
Title to be announced
Speaker: Thomas ZwakaInstitute: Icahn School of Medicine at Mount SinaiHost: Nicolas Rivron
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Speaker: BAUCELLS Julia (Dammermann), GOMEZ SEGALAS Alba (Balzarotti), VOICHEK Maya Shinan (Brennecke)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Functional organization of bacterial chromosomes
Speaker: Virginia LioyInstitute: I2BC, FranceHost: Tobias Viehböck
Human adult neurogenesis
Speaker: Maria LlorensInstitute: CBMHost: Noelia Urban
Title to be announced
Speaker: Arun K. ShuklaInstitute: Indian Institute of TechnologyHost: David Haselbach
Monday Seminar (Internal)
Speaker: DMITRIEV Vladimir (Goloborodko), HISANAGA Tetsuya (Berger), KHALDIEH Nina (Ameres)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Origins of cell diversity in self-organizing multicellular tissues
Speaker: Nicole RepinaInstitute: FMI, BaselHost: Mihaela Pavlicev
Visualization of Macromolecular Assemblies in Meiosis Using Cryo-Electron Tomography
Speaker: Jannik HugenerInstitute: ETH ZürichHost: Joao Matos
Expanding the genetic code - new chemistries and tools for biology
Speaker: Kathrin LangInstitute: ETH ZurichHost: Tim Clausen
Ubiquitin & Friends Symposium 2023
The Ubiquitin & Friends Symposium is an international meeting taking place in the beautiful capital of Austria and aims to bring together scholars from various fields of ubiquitin and protein degradation research in a personal, family-like atmosphere, as suggested by the name.
17th Microsymposium on RNA Biology
The „Microsymposium on RNA Biology“ is an international conference that brings together young scientists, junior and senior group leaders, and company representatives from all over the world to present and discuss their latest findings in the exciting field of small RNAs and beyond. The Microsymposium was founded in 2005 and has established itself as the major small RNA meeting in Europe. It is organized by the four research institutions IMBA, IMP, GMI and the Max Perutz Labs as well as by the RNA community of the Vienna BioCenter.
Title to be announced
Speaker: Luca GiorgettiInstitute: FMI BaselHost: Christa Bücker
Monday Seminar (Internal)
Speaker: SOMMER Theresa (Rivron), SHIRZADIAN YAZD Mehrta (Balzarotti), VERTESY Abel (Knoblich)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
What's the point of chromatin?
Speaker: Tobias WarneckeInstitute: MRC London Institute of Medical Sciences, Imperial College LondonHost: Fred Berger
Control of meiotic crossover placement in Drosophila
Speaker: Jeff SekelskyInstitute: UNC School of MedicineHost: Joao Matos
Title to be announced
Speaker: David KelleyInstitute: Calico LabsHost: Alex Stark
Title to be announced
Speaker: Joanna WysockaInstitute: Stanford School of MedicineHost: Christa Bücker
Monday Seminar (Internal)
Speaker: POLIKARPOVA Anastasia (Tanaka), CHAKRABORTY Oisorjo (Grade), CORSI Flavia (Goloborodko)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Comprehensive understanding of cancer fitness landscape from germline to somatic alterations
Speaker: Solip ParkInstitute: CNIO, SpainHost: Martin Kuhlwilm
Identification of novel ciliogenesis genes using a phylogenetic profiling approach
Speaker: Alex DammermannInstitute: Dept. Microbiology, Immunbiology and Genetics, University ViennaHost: Verena Jantsch
Neuronal Genome Stability and Plasticity
Speaker: Andre NussenzweigInstitute: NIHHost: Jan-Michael Peters
Monday Seminar (Internal)
Speaker: KHAURATOVIC Uladzislava (Matos/Golobordko), SHEN Jingyi (Obenauf), FESSELET Jeanne (Kovarik)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Off the wall: consequences of a cell wall-deficient lifestyle in bacteria
Speaker: Daniel ClaessenInstitute: Leiden UniversityHost: Silvia Bulgheresi
Title to be announced
Speaker: Roger GeigerInstitute: Institute for Research in Biomedicine, BellinzonaHost: Joris Van der Veeken
Probing chromosome mechanics in the interphase nucleus
Speaker: Antoine CoulonInstitute: Institut CurieHost: Anton Goloborodko and Daniel Gerlich
Monday Seminar (Internal)
Speaker: PERNEBRINK Mattias (Tanaka), HOHMANN Ulrich (Brennecke/Plaschka), MANOLOVA Toni (Falk)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
The Earth BioGenome Project: Progress Toward a New Synthesis in Evolution Science
Speaker: Harris LewinInstitute: UC DavisHost: Darrin Schultz and Oleg Simakov
Monday Seminar (Internal)
Speaker: WU Shuangyang (Dolan), SCARAMUZZA Federico (Tessmar), KROGULL Daniel (Burga)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
The recently discovered ties between teeth and infants in human evolution
Speaker: Leslea HluskoInstitute: CENIEHHost: Nicole Grunstra
Characterisation of Vpr1, a novel protein involved in DSB repair
Speaker: Mustafa AlaaboInstitute: Dept. Chromosome Biology, Univ. ViennaHost: Franz Klein
New insights in gene regulation and chromatin folding by enhancers and cohesin
Speaker: Wouter de LaatInstitute: Hubrecht InstituteHost: Christa Bücker
Monday Seminar (Internal)
Speaker: HEIDARI KHOEI Heidar (Rivron), ABDRAKHMANOV Alibek (Dagdas), GALUSKA Philipp (Djinovic)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
Speaker: Daniele CanzioInstitute: UCSFHost: Anton Goloborodko
Monday Seminar (Internal)
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Comprehensive and quantitative characterization of aneuploidy phenotypes
Speaker: Manuela Sophie KollerInstitute: Dept. Chromosome Biology, Univ. ViennaHost: Chris Campbell
Monday Seminar (Internal)
Speaker: JELENIC Stela (Saha), PACHECO FIALLOS Franics Belen (Plaschka), FONTES OLIVEIRA Tiago Manuel (Penninger)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
The Mirage of Biosocial Complexity: Critique and Collaboration Around the Tools of Epigenetics
Speaker: Luca ChiapperinoInstitute: Institute of Social Sciences (ISS), University of LausanneHost: Vienna Open Lab
Monday Seminar (Internal)
Speaker: NAGUMO WONG Sakurako (Knoblich), LORENZO ORTS Laura (Pauli), ROSS James (Burga)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
Speaker: Samer HattarInstitute: NIHHost: Kristin Tessmar
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Title to be announced
Speaker: Anshul KundajeInstitute: Stanford UniversityHost: Alex Stark
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Monday Seminar (Internal)
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Title to be announced
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Speaker: LICHT-MAYER Simon (Penninger), CAYGILL Samuel (Dolan), MIGOTTI Mario (Konrat)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
Speaker: Feng ShaoInstitute: National Institute of Biological Sciences, BeijingHost: Pavel Kovarik
Monday Seminar (Internal)
Speaker: SHUNMUGAM Dhanlakshmi (Baccarini), CECI GINISTRELLI Lavinia (Mendjan), VORLÄNDER Matthias (Plaschka)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
Speaker: Jan LöweInstitute: MRC Laboratory of Molecular BiologyHost: Jan-Michael Peters
Title to be announced
Speaker: Lydia FinleyInstitute: Memorial Sloan Kettering Cancer CenterHost: Johannes Zuber
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Speaker: KOK Jian Yi (Berger), GROH Roan (Dagdas), SODERHOLM Adrian (Versteeg)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
Speaker: Stephan GruberInstitute: University of LausanneHost: Franz Klein
Monday Seminar (Internal)
Speaker: STRAVS Ana (Knoblich), SANCHEZ DE MEDINA HERNANDEZ Victor (Dagdas), HORENKAMP Simone (Tanaka)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: TAVERINI Katherina (Urban), CORIC Aida (Tessmar)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
Speaker: Nancy KlecknerInstitute: Harvard UniversityHost: Franz Klein
Monday Seminar (Internal)
Speaker: GRABARCZYK Daniel (Clausen), PROTELL I DE MONTSERRAT Julia (Brennecke/Plaschka), MANCHENO JUNCOSA Estela (Mendjan)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
Speaker: Edward LemkeInstitute: IMB MainzHost: David Haselbach
Monday Seminar (Internal)
Speaker: ATTRILL Sarah (Dolan), UIJTTEWAAL Esther (Elling), SCIBISZ Grzegorz (Karagöz)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: DOLESCHALL Balint (Knoblich), FENG Sonjie (Bücker), BOURGUET Pierre (Berger)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
Speaker: Rotem SorekInstitute: Weizmann Institute of Science, RehovotHost: Julius Brennecke
Monday Seminar (Internal)
Speaker: KRUMWIEDE Luisa (Gaidt), CASEY Chloe (Dolan), KAPRAL Thomas (Zagrovic)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: KOBAKHIDZE George (Dong), ANGELOPOULOU Eleni (Ellis), PACHANO Tomas (Stark)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
Speaker: Stephan GrillInstitute: MPI of Molecular Cell Biology and GeneticsHost: Clemens Plaschka
Monday Seminar (Internal)
Speaker: RAMIREZ America (Köhler), VÖLKL Isabella (Bücker), HOANG Oi Pui (Technau)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
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Monday Seminar (Internal)
Speaker: LEITNER Moritz (Martinez), VOGEL Alexander (Yudushkin), KETTEL Paulina (Karagöz)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
Speaker: Martin HetzerInstitute: IST AustriaHost: Jürgen Knoblich
Monday Seminar (Internal)
Speaker: TSAREV Aleksandr (Ameres), FIESELER Charlie (Zimmer), ABESAMIS Kim Ivan (Dong)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
Speaker: Laurent NguyenInstitute: University of LiegeHost: Noelia Urban
Monday Seminar (Internal)
Speaker: KLEIFELD Justus (Urban), ORLIC Lucija (Matos)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
Speaker: Ian HicksonInstitute: University of CopenhagenHost: Joao Matos
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Monday Seminar (Internal)
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Monday Seminar (Internal)
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Monday Seminar (Internal)
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Monday Seminar (Internal)
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Monday Seminar (Internal)
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Monday Seminar (Internal)
Speaker: AYALA MUNOZ Farja (Plaschka), VETRANO Pamela (Ramundo), YU Changwei (Brennecke)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: KONSTANTINOU Andri (Obenauf), NAVA GARCIA Marintia (Dagdas), WOLFF Uyen Le Phuong (Jantsch V.)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: HARTMANN Felix (Matos), PASSERA Alessandro (Balzarotti), SANCHEZ BURGOS Laura (Obenauf)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: HAIDER Jakob (Gaidt), HODAKOVA Zuzana (Haselbach), MYLARSHCHIKOV Dmitry (Gerlich)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
Speaker: Johannes WalterInstitute: Harvard Medical SchoolHost: Jan-Michael Peters
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Speaker: PIECH Lucas (Leonard), DE LA CONCEPCION Juan Carlos (Dagdas), POPOVA Mariia (Peters)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
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Speaker: VELETI Lalitha (Pauli), FORISCH Stephan (Elling), NAAS Julia (Van Haeseler)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
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Monday Seminar (Internal)
Speaker: PROTSENKO Liudmila (Brennecke), SHETTY Kavya (Hein), BASSAT Elad (Tanaka)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
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