Professional Education


  • Doctor of Philosophy, University of Cologne (2012)
  • PostDoc, Plant Systems Biology - VIB - Ghent University (2015)
  • Staatsexamen, Cologne University of Applied Sciences (2008)

Stanford Advisors


All Publications


  • Specialization of CDK regulation under DNA damage. Cell cycle Weimer, A. K., Biedermann, S., Schnittger, A. 2017; 16 (2): 143-144

    View details for DOI 10.1080/15384101.2016.1235852

    View details for PubMedID 27687239

    View details for PubMedCentralID PMC5283820

  • Phosphorylation of MAP65-1 by Arabidopsis Aurora Kinases Is Required for Efficient Cell Cycle Progression PLANT PHYSIOLOGY Boruc, J., Weimer, A. K., Stoppin-Mellet, V., Mylle, E., Kosetsu, K., Cedeno, C., Jaquinod, M., Njo, M., De Milde, L., Tompa, P., Gonzalez, N., Inze, D., Beeckman, T., Vantard, M., Van Damme, D. 2017; 173 (1): 582-599

    Abstract

    Aurora kinases are key effectors of mitosis. Plant Auroras are functionally divided into two clades. The alpha Auroras (Aurora1 and Aurora2) associate with the spindle and the cell plate and are implicated in controlling formative divisions throughout plant development. The beta Aurora (Aurora3) localizes to centromeres and likely functions in chromosome separation. In contrast to the wealth of data available on the role of Aurora in other kingdoms, knowledge on their function in plants is merely emerging. This is exemplified by the fact that only histone H3 and the plant homolog of TPX2 have been identified as Aurora substrates in plants. Here we provide biochemical, genetic, and cell biological evidence that the microtubule-bundling protein MAP65-1-a member of the MAP65/Ase1/PRC1 protein family, implicated in central spindle formation and cytokinesis in animals, yeasts, and plants-is a genuine substrate of alpha Aurora kinases. MAP65-1 interacts with Aurora1 in vivo and is phosphorylated on two residues at its unfolded tail domain. Its overexpression and down-regulation antagonistically affect the alpha Aurora double mutant phenotypes. Phospho-mutant analysis shows that Aurora contributes to the microtubule bundling capacity of MAP65-1 in concert with other mitotic kinases.

    View details for DOI 10.1104/pp.16.01602

    View details for Web of Science ID 000394135800043

    View details for PubMedID 27879390

  • The plant-specific CDKB1-CYCB1 complex mediates homologous recombination repair in Arabidopsis EMBO JOURNAL Weimer, A. K., Biedermann, S., Harashima, H., Roodbarkelari, F., Takahashi, N., Foreman, J., Guan, Y., Pochon, G., Heese, M., van Damme, D., Sugimoto, K., Koncz, C., Doerner, P., Umeda, M., Schnittger, A. 2016; 35 (19): 2068-2086

    Abstract

    Upon DNA damage, cyclin-dependent kinases (CDKs) are typically inhibited to block cell division. In many organisms, however, it has been found that CDK activity is required for DNA repair, especially for homology-dependent repair (HR), resulting in the conundrum how mitotic arrest and repair can be reconciled. Here, we show that Arabidopsis thaliana solves this dilemma by a division of labor strategy. We identify the plant-specific B1-type CDKs (CDKB1s) and the class of B1-type cyclins (CYCB1s) as major regulators of HR in plants. We find that RADIATION SENSITIVE 51 (RAD51), a core mediator of HR, is a substrate of CDKB1-CYCB1 complexes. Conversely, mutants in CDKB1 and CYCB1 fail to recruit RAD51 to damaged DNA CYCB1;1 is specifically activated after DNA damage and we show that this activation is directly controlled by SUPPRESSOR OF GAMMA RESPONSE 1 (SOG1), a transcription factor that acts similarly to p53 in animals. Thus, while the major mitotic cell-cycle activity is blocked after DNA damage, CDKB1-CYCB1 complexes are specifically activated to mediate HR.

    View details for DOI 10.15252/embj.201593083

    View details for Web of Science ID 000385707500004

    View details for PubMedID 27497297

    View details for PubMedCentralID PMC5048351

  • Aurora Kinases Throughout Plant Developoment TRENDS IN PLANT SCIENCE Weimer, A. K., Demidov, D., Lermontova, I., Beeckman, T., Van Damme, D. 2016; 21 (1): 69-79

    Abstract

    Aurora kinases are evolutionarily conserved key mitotic determinants in all eukaryotes. Yeasts contain a single Aurora kinase, whereas multicellular eukaryotes have at least two functionally diverged members. The involvement of Aurora kinases in human cancers has provided an in-depth mechanistic understanding of their roles throughout cell division in animal and yeast models. By contrast, understanding Aurora kinase function in plants is only starting to emerge. Nevertheless, genetic, cell biological, and biochemical approaches have revealed functional diversification between the plant Aurora kinases and suggest a role in formative (asymmetric) divisions, chromatin modification, and genome stability. This review provides an overview of the accumulated knowledge on the function of plant Aurora kinases as well as some major challenges for the future.

    View details for DOI 10.1016/j.tplants.2015.10.001

    View details for Web of Science ID 000369199200010

    View details for PubMedID 26616196

  • RETINOBLASTOMA RELATED1 Regulates Asymmetric Cell Divisions in Arabidopsis PLANT CELL Weimer, A. K., Nowack, M. K., Bouyer, D., Zhao, X., Harashima, H., Naseer, S., De Winter, F., Dissmeyer, N., Geldner, N., Schnittger, A. 2012; 24 (10): 4083-4095

    Abstract

    Formative, also called asymmetric, cell divisions produce daughter cells with different identities. Like other divisions, formative divisions rely first of all on the cell cycle machinery with centrally acting cyclin-dependent kinases (CDKs) and their cyclin partners to control progression through the cell cycle. However, it is still largely obscure how developmental cues are translated at the cellular level to promote asymmetric divisions. Here, we show that formative divisions in the shoot and root of the flowering plant Arabidopsis thaliana are controlled by a common mechanism that relies on the activity level of the Cdk1 homolog CDKA;1, with medium levels being sufficient for symmetric divisions but high levels being required for formative divisions. We reveal that the function of CDKA;1 in asymmetric cell divisions operates through a transcriptional regulation system that is mediated by the Arabidopsis Retinoblastoma homolog RBR1. RBR1 regulates not only cell cycle genes, but also, independent of the cell cycle transcription factor E2F, genes required for formative divisions and cell fate acquisition, thus directly linking cell proliferation with differentiation. This mechanism allows the implementation of spatial information, in the form of high kinase activity, with intracellular gating of developmental decisions.

    View details for DOI 10.1105/tpc.112.104620

    View details for Web of Science ID 000312378300017

    View details for PubMedID 23104828

  • A General G1/S-Phase Cell-Cycle Control Module in the Flowering Plant Arabidopsis thaliana PLOS GENETICS Zhao, X., Harashima, H., Dissmeyer, N., Pusch, S., Weimer, A. K., Bramsiepe, J., Bouyer, D., Rademacher, S., Nowack, M. K., Novak, B., Sprunck, S., Schnittger, A. 2012; 8 (8)

    Abstract

    The decision to replicate its DNA is of crucial importance for every cell and, in many organisms, is decisive for the progression through the entire cell cycle. A comparison of animals versus yeast has shown that, although most of the involved cell-cycle regulators are divergent in both clades, they fulfill a similar role and the overall network topology of G1/S regulation is highly conserved. Using germline development as a model system, we identified a regulatory cascade controlling entry into S phase in the flowering plant Arabidopsis thaliana, which, as a member of the Plantae supergroup, is phylogenetically only distantly related to Opisthokonts such as yeast and animals. This module comprises the Arabidopsis homologs of the animal transcription factor E2F, the plant homolog of the animal transcriptional repressor Retinoblastoma (Rb)-related 1 (RBR1), the plant-specific F-box protein F-BOX-LIKE 17 (FBL17), the plant specific cyclin-dependent kinase (CDK) inhibitors KRPs, as well as CDKA;1, the plant homolog of the yeast and animal Cdc2Ôü║/Cdk1 kinases. Our data show that the principle of a double negative wiring of Rb proteins is highly conserved, likely representing a universal mechanism in eukaryotic cell-cycle control. However, this negative feedback of Rb proteins is differently implemented in plants as it is brought about through a quadruple negative regulation centered around the F-box protein FBL17 that mediates the degradation of CDK inhibitors but is itself directly repressed by Rb. Biomathematical simulations and subsequent experimental confirmation of computational predictions revealed that this regulatory circuit can give rise to hysteresis highlighting the here identified dosage sensitivity of CDK inhibitors in this network.

    View details for DOI 10.1371/journal.pgen.1002847

    View details for Web of Science ID 000308529300011

    View details for PubMedID 22879821

  • Genetic Framework of Cyclin-Dependent Kinase Function in Arabidopsis DEVELOPMENTAL CELL Nowack, M. K., Harashima, H., Dissmeyer, N., Zhao, X., Bouyer, D., Weimer, A. K., De Winter, F., Yang, F., Schnittger, A. 2012; 22 (5): 1030-1040

    Abstract

    Cyclin-dependent kinases (CDKs) are at the heart of eukaryotic cell-cycle control. The yeast Cdc2/CDC28 PSTAIRE kinase and its orthologs such as the mammalian Cdk1 have been found to be indispensable for cell-cycle progression in all eukaryotes investigated so far. CDKA;1 is the only PSTAIRE kinase in the flowering plant Arabidopsis and can rescue Cdc2/CDC28 mutants. Here, we show that cdka;1 null mutants are viable but display specific cell-cycle and developmental defects, e.g., in S phase entry and stem cell maintenance. We unravel that the crucial function of CDKA;1 is the control of the plant Retinoblastoma homolog RBR1 and that codepletion of RBR1 and CDKA;1 rescued most defects of cdka;1 mutants. Our work further revealed a basic cell-cycle control system relying on two plant-specific B1-type CDKs, and the triple cdk mutants displayed an early germline arrest. Taken together, our data indicate divergent functional differentiation of Cdc2-type kinases during eukaryote evolution.

    View details for DOI 10.1016/j.devcel.2012.02.015

    View details for Web of Science ID 000304291700015

    View details for PubMedID 22595674

  • The Arabidopsis thaliana Checkpoint Kinase WEE1 Protects against Premature Vascular Differentiation during Replication Stress PLANT CELL Cools, T., Iantcheva, A., Weimer, A. K., Boens, S., Takahashi, N., Maes, S., Van Den Daele, H., Van Isterdael, G., Schnittger, A., De Veylder, L. 2011; 23 (4): 1435-1448

    Abstract

    A sessile lifestyle forces plants to respond promptly to factors that affect their genomic integrity. Therefore, plants have developed checkpoint mechanisms to arrest cell cycle progression upon the occurrence of DNA stress, allowing the DNA to be repaired before onset of division. Previously, the WEE1 kinase had been demonstrated to be essential for delaying progression through the cell cycle in the presence of replication-inhibitory drugs, such as hydroxyurea. To understand the severe growth arrest of WEE1-deficient plants treated with hydroxyurea, a transcriptomics analysis was performed, indicating prolonged S-phase duration. A role for WEE1 during S phase was substantiated by its specific accumulation in replicating nuclei that suffered from DNA stress. Besides an extended replication phase, WEE1 knockout plants accumulated dead cells that were associated with premature vascular differentiation. Correspondingly, plants without functional WEE1 ectopically expressed the vascular differentiation marker VND7, and their vascular development was aberrant. We conclude that the growth arrest of WEE1-deficient plants is due to an extended cell cycle duration in combination with a premature onset of vascular cell differentiation. The latter implies that the plant WEE1 kinase acquired an indirect developmental function that is important for meristem maintenance upon replication stress.

    View details for DOI 10.1105/tpc.110.082768

    View details for Web of Science ID 000291000500022

    View details for PubMedID 21498679

  • The regulatory network of cell-cycle progression is fundamentally different in plants versus yeast or metazoans. Plant signaling & behavior Dissmeyer, N., Weimer, A. K., De Veylder, L., Novak, B., Schnittger, A. 2010; 5 (12): 1613-1618

    Abstract

    Plant growth and proliferation control is coming into a global focus due to recent ecological and economical developments. Plants represent not only the largest food supply for mankind but also may serve as a global source of renewable energies. However, plant breeding has to accomplish a tremendous boost in yield to match the growing demand of a still rapidly increasing human population. Moreover, breeding has to adjust to changing environmental conditions, in particular increased drought. Regulation of cell-cycle control is a major determinant of plant growth and therefore an obvious target for plant breeding. Furthermore, cell-cycle control is also crucial for the DNA damage response, for instance upon irradiation. Thus, an in-depth understanding of plant cell-cycle regulation is of importance beyond a scientific point of view. The mere presence of many conserved core cell-cycle regulators, e.g. CDKs, cyclins, or CDK inhibitors, has formed the idea that the cell cycle in plants is exactly or at least very similarly controlled as in yeast or human cells. Here together with a recent publication we demonstrate that this dogma is not true and show that the control of entry into mitosis is fundamentally different in plants versus yeast or metazoans. Our findings build an important base for the understanding and ultimate modulation of plant growth not only during unperturbed but also under harsh environmental conditions.

    View details for PubMedID 21139435

  • Control of Cell Proliferation, Organ Growth, and DNA Damage Response Operate Independently of Dephosphorylation of the Arabidopsis Cdk1 Homolog CDKA;1 PLANT CELL Dissmeyer, N., Weimer, A. K., Pusch, S., De Schutter, K., Kamei, C. L., Nowack, M. K., Novak, B., Duan, G., Zhu, Y., De Veylder, L., Schnittger, A. 2009; 21 (11): 3641-3654

    Abstract

    Entry into mitosis is universally controlled by cyclin-dependent kinases (CDKs). A key regulatory event in metazoans and fission yeast is CDK activation by the removal of inhibitory phosphate groups in the ATP binding pocket catalyzed by Cdc25 phosphatases. In contrast with other multicellular organisms, we show here that in the flowering plant Arabidopsis thaliana, cell cycle control does not depend on sudden changes in the phosphorylation pattern of the PSTAIRE-containing Cdk1 homolog CDKA;1. Consistently, we found that neither mutants in a previously identified CDC25 candidate gene nor plants in which it is overexpressed display cell cycle defects. Inhibitory phosphorylation of CDKs is also the key event in metazoans to arrest cell cycle progression upon DNA damage. However, we show here that the DNA damage checkpoint in Arabidopsis can also operate independently of the phosphorylation of CDKA;1. These observations reveal a surprising degree of divergence in the circuitry of highly conserved core cell cycle regulators in multicellular organisms. Based on biomathematical simulations, we propose a plant-specific model of how progression through the cell cycle could be wired in Arabidopsis.

    View details for DOI 10.1105/tpc.109.070417

    View details for Web of Science ID 000273235600020

    View details for PubMedID 19948791