Honors & Awards


  • The Walter V. and Idun Berry Postdoctoral Fellowship, Stanford University (09/2016-08/2017)
  • School of Medicine Dean's Postdoctoral Fellowship, Stanford University School of Medicine (01/2016-12/2016)

Boards, Advisory Committees, Professional Organizations


  • Member, OEGMBT Austrian Association of Molecular Life Sciences and Biotechnology (2015 - Present)
  • Member, FEBS The Federation of European Biochemical Societies (2016 - Present)

Professional Education


  • Magister, Universitat Wien (2009)
  • Doctor of Philosophy, Universitat Wien (2013)

Stanford Advisors


All Publications


  • Rapid movement and transcriptional re-localization of human cohesin on DNA EMBO JOURNAL Davidson, I. F., Goetz, D., Zaczek, M. P., Molodtsov, M. I., in't Veld, P. J., Weissmann, F., Litos, G., Cisneros, D. A., Ocampo-Hafalla, M., Ladurner, R., Uhlmann, F., Vaziri, A., Peters, J. 2016; 35 (24): 2671-2685

    Abstract

    The spatial organization, correct expression, repair, and segregation of eukaryotic genomes depend on cohesin, ring-shaped protein complexes that are thought to function by entrapping DNA It has been proposed that cohesin is recruited to specific genomic locations from distal loading sites by an unknown mechanism, which depends on transcription, and it has been speculated that cohesin movements along DNA could create three-dimensional genomic organization by loop extrusion. However, whether cohesin can translocate along DNA is unknown. Here, we used single-molecule imaging to show that cohesin can diffuse rapidly on DNA in a manner consistent with topological entrapment and can pass over some DNA-bound proteins and nucleosomes but is constrained in its movement by transcription and DNA-bound CCCTC-binding factor (CTCF). These results indicate that cohesin can be positioned in the genome by moving along DNA, that transcription can provide directionality to these movements, that CTCF functions as a boundary element for moving cohesin, and they are consistent with the hypothesis that cohesin spatially organizes the genome via loop extrusion.

    View details for DOI 10.15252/embj.201695402

    View details for Web of Science ID 000390948700008

    View details for PubMedID 27799150

    View details for PubMedCentralID PMC5167347

  • MIS12/MIND Control at the Kinetochore. Cell Ladurner, R., Straight, A. F. 2016; 167 (4): 889-891

    Abstract

    Kinetochores are complex multiprotein machines that link chromosomes to dynamic microtubules for chromosome segregation. Two studies in Cell reveal the structure of the human MIS12 and budding yeast MIND kinetochore complexes and the regulatory mechanisms that enable them to link chromosomes to microtubules during mitosis.

    View details for DOI 10.1016/j.cell.2016.10.036

    View details for PubMedID 27814517

  • Sororin actively maintains sister chromatid cohesion EMBO JOURNAL Ladurner, R., Kreidl, E., Ivanov, M. P., Ekker, H., Idarraga-Amado, M. H., Busslinger, G. A., Wutz, G., Cisneros, D. A., Peters, J. 2016; 35 (6): 635-653

    Abstract

    Cohesion between sister chromatids is established during DNA replication but needs to be maintained to enable proper chromosome-spindle attachments in mitosis or meiosis. Cohesion is mediated by cohesin, but also depends on cohesin acetylation and sororin. Sororin contributes to cohesion by stabilizing cohesin on DNA. Sororin achieves this by inhibiting WAPL, which otherwise releases cohesin from DNA and destroys cohesion. Here we describe mouse models which enable the controlled depletion of sororin by gene deletion or auxin-induced degradation. We show that sororin is essential for embryonic development, cohesion maintenance, and proper chromosome segregation. We further show that the acetyltransferases ESCO1 and ESCO2 are essential for stabilizing cohesin on chromatin, that their only function in this process is to acetylate cohesin's SMC3 subunit, and that DNA replication is also required for stable cohesin-chromatin interactions. Unexpectedly, we find that sororin interacts dynamically with the cohesin complexes it stabilizes. This implies that sororin recruitment to cohesin does not depend on the DNA replication machinery or process itself, but on a property that cohesin acquires during cohesion establishment.

    View details for Web of Science ID 000372254700007

    View details for PubMedID 26903600

  • Characterization of a DNA exit gate in the human cohesin ring. Science Huis In 't Veld, P. J., Herzog, F., Ladurner, R., Davidson, I. F., Piric, S., Kreidl, E., Bhaskara, V., Aebersold, R., Peters, J. 2014; 346 (6212): 968-972

    Abstract

    Chromosome segregation depends on sister chromatid cohesion mediated by cohesin. The cohesin subunits Smc1, Smc3, and Scc1 form tripartite rings that are thought to open at distinct sites to allow entry and exit of DNA. However, direct evidence for the existence of open forms of cohesin is lacking. We found that cohesin's proposed DNA exit gate is formed by interactions between Scc1 and the coiled-coil region of Smc3. Mutation of this interface abolished cohesin's ability to stably associate with chromatin and to mediate cohesion. Electron microscopy revealed that weakening of the Smc3-Scc1 interface resulted in opening of cohesin rings, as did proteolytic cleavage of Scc1. These open forms may resemble intermediate states of cohesin normally generated by the release factor Wapl and the protease separase, respectively.

    View details for DOI 10.1126/science.1256904

    View details for PubMedID 25414306

  • SNW1 enables sister chromatid cohesion by mediating the splicing of sororin and APC2 pre-mRNAs EMBO JOURNAL van der Lelij, P., Stocsits, R. R., Ladurner, R., Petzold, G., Kreidl, E., Koch, B., Schmitz, J., Neumann, B., Ellenberg, J., Peters, J. 2014; 33 (22): 2643-2658

    Abstract

    Although splicing is essential for the expression of most eukaryotic genes, inactivation of splicing factors causes specific defects in mitosis. The molecular cause of this defect is unknown. Here, we show that the spliceosome subunits SNW1 and PRPF8 are essential for sister chromatid cohesion in human cells. A transcriptome-wide analysis revealed that SNW1 or PRPF8 depletion affects the splicing of specific introns in a subset of pre-mRNAs, including pre-mRNAs encoding the cohesion protein sororin and the APC/C subunit APC2. SNW1 depletion causes cohesion defects predominantly by reducing sororin levels, which causes destabilisation of cohesin on DNA. SNW1 depletion also reduces APC/C activity and contributes to cohesion defects indirectly by delaying mitosis and causing "cohesion fatigue". Simultaneous expression of sororin and APC2 from intron-less cDNAs restores cohesion in SNW1-depleted cells. These results indicate that the spliceosome is required for mitosis because it enables expression of genes essential for cohesion. Our transcriptome-wide identification of retained introns in SNW1- and PRPF8-depleted cells may help to understand the aetiology of diseases associated with splicing defects, such as retinosa pigmentosum and cancer.

    View details for Web of Science ID 000345299300007

    View details for PubMedID 25257309

  • Cohesin's ATPase Activity Couples Cohesin Loading onto DNA with Smc3 Acetylation CURRENT BIOLOGY Ladurner, R., Bhaskara, V., in't Veld, P. J., Davidson, I. F., Kreidl, E., Petzold, G., Peters, J. 2014; 24 (19): 2228-2237

    Abstract

    Cohesin mediates sister chromatid cohesion by topologically entrapping sister DNA molecules inside its ring structure. Cohesin is loaded onto DNA by the Scc2/NIPBL-Scc4/MAU2-loading complex in a manner that depends on the adenosine triphosphatase (ATPase) activity of cohesin's Smc1 and Smc3 subunits. Subsequent cohesion establishment during DNA replication depends on Smc3 acetylation by Esco1 and Esco2 and on recruitment of sororin, which "locks" cohesin on DNA by inactivating the cohesin release factor Wapl.Human cohesin ATPase mutants associate transiently with DNA in a manner that depends on the loading complex but cannot be stabilized on chromatin by depletion of Wapl. These mutants cannot be acetylated, fail to interact with sororin, and do not mediate cohesion. The absence of Smc3 acetylation in the ATPase mutants is not a consequence of their transient association with DNA but is directly caused by their inability to hydrolyze ATP because acetylation of wild-type cohesin also depends on ATP hydrolysis.Our data indicate that cohesion establishment involves the following steps. First, cohesin transiently associates with DNA in a manner that depends on the loading complex. Subsequently, ATP hydrolysis by cohesin leads to entrapment of DNA and converts Smc3 into a state that can be acetylated. Finally, Smc3 acetylation leads to recruitment of sororin, inhibition of Wapl, and stabilization of cohesin on DNA. Our finding that cohesin's ATPase activity is required for both cohesin loading and Smc3 acetylation raises the possibility that cohesion establishment is directly coupled to the reaction in which cohesin entraps DNA.

    View details for DOI 10.1016/j.cub.2014.08.011

    View details for Web of Science ID 000342747600017

    View details for PubMedID 25220052

  • APC15 mediates CDC20 autoubiquitylation by APC/C-MCC and disassembly of the mitotic checkpoint complex NATURE STRUCTURAL & MOLECULAR BIOLOGY Uzunova, K., Dye, B. T., Schutz, H., Ladurner, R., Petzold, G., Toyoda, Y., Jarvis, M. A., Brown, N. G., Poser, I., Novatchkova, M., Mechtler, K., Hyman, A. A., Stark, H., Schulman, B. A., Peters, J. 2012; 19 (11): 1116-?

    Abstract

    The anaphase-promoting complex/cyclosome (APC/C) bound to CDC20 (APC/C(CDC20)) initiates anaphase by ubiquitylating B-type cyclins and securin. During chromosome bi-orientation, CDC20 assembles with MAD2, BUBR1 and BUB3 into a mitotic checkpoint complex (MCC) that inhibits substrate recruitment to the APC/C. APC/C activation depends on MCC disassembly, which was proposed to require CDC20 autoubiquitylation. Here we characterize APC15, a human APC/C subunit related to yeast Mnd2. APC15 is located near APC/C's MCC binding site; it is required for APC/C-bound MCC (APC/C(MCC))-dependent CDC20 autoubiquitylation and degradation and for timely anaphase initiation but is dispensable for substrate ubiquitylation by APC/C(CDC20) and APC/C(CDH1). Our results support the model wherein MCC is continuously assembled and disassembled to enable rapid activation of APC/C(CDC20) and CDC20 autoubiquitylation promotes MCC disassembly. We propose that APC15 and Mnd2 negatively regulate APC/C coactivators and report generation of recombinant human APC/C.

    View details for DOI 10.1038/nsmb.2412

    View details for Web of Science ID 000310788800010

    View details for PubMedID 23007861

  • Sororin Mediates Sister Chromatid Cohesion by Antagonizing Wapl CELL Nishiyama, T., Ladurner, R., Schmitz, J., Kreidl, E., Schleiffer, A., Bhaskara, V., Bando, M., Shirahige, K., Hyman, A. A., Mechtler, K., Peters, J. 2010; 143 (5): 737-749

    Abstract

    Sister chromatid cohesion is essential for chromosome segregation and is mediated by cohesin bound to DNA. Cohesin-DNA interactions can be reversed by the cohesion-associated protein Wapl, whereas a stably DNA-bound form of cohesin is thought to mediate cohesion. In vertebrates, Sororin is essential for cohesion and stable cohesin-DNA interactions, but how Sororin performs these functions is unknown. We show that DNA replication and cohesin acetylation promote binding of Sororin to cohesin, and that Sororin displaces Wapl from its binding partner Pds5. In the absence of Wapl, Sororin becomes dispensable for cohesion. We propose that Sororin maintains cohesion by inhibiting Wapl's ability to dissociate cohesin from DNA. Sororin has only been identified in vertebrates, but we show that many invertebrate species contain Sororin-related proteins, and that one of these, Dalmatian, is essential for cohesion in Drosophila. The mechanism we describe here may therefore be widely conserved among different species.

    View details for DOI 10.1016/j.cell.2010.10.031

    View details for Web of Science ID 000284583500016

    View details for PubMedID 21111234