@article{11060, abstract = {The inner nuclear membrane (INM) is a subdomain of the endoplasmic reticulum (ER) that is gated by the nuclear pore complex. It is unknown whether proteins of the INM and ER are degraded through shared or distinct pathways in mammalian cells. We applied dynamic proteomics to profile protein half-lives and report that INM and ER residents turn over at similar rates, indicating that the INM’s unique topology is not a barrier to turnover. Using a microscopy approach, we observed that the proteasome can degrade INM proteins in situ. However, we also uncovered evidence for selective, vesicular transport-mediated turnover of a single INM protein, emerin, that is potentiated by ER stress. Emerin is rapidly cleared from the INM by a mechanism that requires emerin’s LEM domain to mediate vesicular trafficking to lysosomes. This work demonstrates that the INM can be dynamically remodeled in response to environmental inputs.}, author = {Buchwalter, Abigail and Schulte, Roberta and Tsai, Hsiao and Capitanio, Juliana and HETZER, Martin W}, issn = {2050-084X}, journal = {eLife}, keywords = {General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, General Medicine, General Neuroscience}, publisher = {eLife Sciences Publications}, title = {{Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stress}}, doi = {10.7554/elife.49796}, volume = {8}, year = {2019}, } @article{11062, abstract = {Most neurons are not replaced during an animal’s lifetime. This nondividing state is characterized by extreme longevity and age-dependent decline of key regulatory proteins. To study the lifespans of cells and proteins in adult tissues, we combined isotope labeling of mice with a hybrid imaging method (MIMS-EM). Using 15N mapping, we show that liver and pancreas are composed of cells with vastly different ages, many as old as the animal. Strikingly, we also found that a subset of fibroblasts and endothelial cells, both known for their replicative potential, are characterized by the absence of cell division during adulthood. In addition, we show that the primary cilia of beta cells and neurons contains different structural regions with vastly different lifespans. Based on these results, we propose that age mosaicism across multiple scales is a fundamental principle of adult tissue, cell, and protein complex organization.}, author = {Arrojo e Drigo, Rafael and Lev-Ram, Varda and Tyagi, Swati and Ramachandra, Ranjan and Deerinck, Thomas and Bushong, Eric and Phan, Sebastien and Orphan, Victoria and Lechene, Claude and Ellisman, Mark H. and HETZER, Martin W}, issn = {1550-4131}, journal = {Cell Metabolism}, keywords = {Cell Biology, Molecular Biology, Physiology}, number = {2}, pages = {343--351.e3}, publisher = {Elsevier}, title = {{Age mosaicism across multiple scales in adult tissues}}, doi = {10.1016/j.cmet.2019.05.010}, volume = {30}, year = {2019}, } @article{8405, abstract = {Atomic-resolution structure determination is crucial for understanding protein function. Cryo-EM and NMR spectroscopy both provide structural information, but currently cryo-EM does not routinely give access to atomic-level structural data, and, generally, NMR structure determination is restricted to small (<30 kDa) proteins. We introduce an integrated structure determination approach that simultaneously uses NMR and EM data to overcome the limits of each of these methods. The approach enables structure determination of the 468 kDa large dodecameric aminopeptidase TET2 to a precision and accuracy below 1 Å by combining secondary-structure information obtained from near-complete magic-angle-spinning NMR assignments of the 39 kDa-large subunits, distance restraints from backbone amides and ILV methyl groups, and a 4.1 Å resolution EM map. The resulting structure exceeds current standards of NMR and EM structure determination in terms of molecular weight and precision. Importantly, the approach is successful even in cases where only medium-resolution cryo-EM data are available.}, author = {Gauto, Diego F. and Estrozi, Leandro F. and Schwieters, Charles D. and Effantin, Gregory and Macek, Pavel and Sounier, Remy and Sivertsen, Astrid C. and Schmidt, Elena and Kerfah, Rime and Mas, Guillaume and Colletier, Jacques-Philippe and Güntert, Peter and Favier, Adrien and Schoehn, Guy and Schanda, Paul and Boisbouvier, Jerome}, issn = {2041-1723}, journal = {Nature Communications}, keywords = {General Biochemistry, Genetics and Molecular Biology, General Physics and Astronomy, General Chemistry}, publisher = {Springer Nature}, title = {{Integrated NMR and cryo-EM atomic-resolution structure determination of a half-megadalton enzyme complex}}, doi = {10.1038/s41467-019-10490-9}, volume = {10}, year = {2019}, } @article{9018, abstract = {Anti-silencing function 1 (ASF1) is a conserved H3-H4 histone chaperone involved in histone dynamics during replication, transcription, and DNA repair. Overexpressed in proliferating tissues including many tumors, ASF1 has emerged as a promising therapeutic target. Here, we combine structural, computational, and biochemical approaches to design peptides that inhibit the ASF1-histone interaction. Starting from the structure of the human ASF1-histone complex, we developed a rational design strategy combining epitope tethering and optimization of interface contacts to identify a potent peptide inhibitor with a dissociation constant of 3 nM. When introduced into cultured cells, the inhibitors impair cell proliferation, perturb cell-cycle progression, and reduce cell migration and invasion in a manner commensurate with their affinity for ASF1. Finally, we find that direct injection of the most potent ASF1 peptide inhibitor in mouse allografts reduces tumor growth. Our results open new avenues to use ASF1 inhibitors as promising leads for cancer therapy.}, author = {Bakail, May M and Gaubert, Albane and Andreani, Jessica and Moal, Gwenaëlle and Pinna, Guillaume and Boyarchuk, Ekaterina and Gaillard, Marie-Cécile and Courbeyrette, Regis and Mann, Carl and Thuret, Jean-Yves and Guichard, Bérengère and Murciano, Brice and Richet, Nicolas and Poitou, Adeline and Frederic, Claire and Le Du, Marie-Hélène and Agez, Morgane and Roelants, Caroline and Gurard-Levin, Zachary A. and Almouzni, Geneviève and Cherradi, Nadia and Guerois, Raphael and Ochsenbein, Françoise}, issn = {2451-9456}, journal = {Cell Chemical Biology}, keywords = {Clinical Biochemistry, Molecular Medicine, Biochemistry, Molecular Biology, Pharmacology, Drug Discovery}, number = {11}, pages = {1573--1585.e10}, publisher = {Elsevier}, title = {{Design on a rational basis of high-affinity peptides inhibiting the histone chaperone ASF1}}, doi = {10.1016/j.chembiol.2019.09.002}, volume = {26}, year = {2019}, } @article{9060, abstract = {Molecular motors are essential to the living, generating fluctuations that boost transport and assist assembly. Active colloids, that consume energy to move, hold similar potential for man-made materials controlled by forces generated from within. Yet, their use as a powerhouse in materials science lacks. Here we show a massive acceleration of the annealing of a monolayer of passive beads by moderate addition of self-propelled microparticles. We rationalize our observations with a model of collisions that drive active fluctuations and activate the annealing. The experiment is quantitatively compared with Brownian dynamic simulations that further unveil a dynamical transition in the mechanism of annealing. Active dopants travel uniformly in the system or co-localize at the grain boundaries as a result of the persistence of their motion. Our findings uncover the potential of internal activity to control materials and lay the groundwork for the rise of materials science beyond equilibrium.}, author = {Ramananarivo, Sophie and Ducrot, Etienne and Palacci, Jérémie A}, issn = {2041-1723}, journal = {Nature Communications}, keywords = {General Biochemistry, Genetics and Molecular Biology, General Physics and Astronomy, General Chemistry}, number = {1}, publisher = {Springer Nature}, title = {{Activity-controlled annealing of colloidal monolayers}}, doi = {10.1038/s41467-019-11362-y}, volume = {10}, year = {2019}, } @article{10355, abstract = {The molecular machinery of life is largely created via self-organisation of individual molecules into functional assemblies. Minimal coarse-grained models, in which a whole macromolecule is represented by a small number of particles, can be of great value in identifying the main driving forces behind self-organisation in cell biology. Such models can incorporate data from both molecular and continuum scales, and their results can be directly compared to experiments. Here we review the state of the art of models for studying the formation and biological function of macromolecular assemblies in living organisms. We outline the key ingredients of each model and their main findings. We illustrate the contribution of this class of simulations to identifying the physical mechanisms behind life and diseases, and discuss their future developments.}, author = {Hafner, Anne E and Krausser, Johannes and Šarić, Anđela}, issn = {0959-440X}, journal = {Current Opinion in Structural Biology}, keywords = {molecular biology, structural biology}, pages = {43--52}, publisher = {Elsevier}, title = {{Minimal coarse-grained models for molecular self-organisation in biology}}, doi = {10.1016/j.sbi.2019.05.018}, volume = {58}, year = {2019}, } @article{12190, abstract = {Meiotic crossover frequency varies within genomes, which influences genetic diversity and adaptation. In turn, genetic variation within populations can act to modify crossover frequency in cis and trans. To identify genetic variation that controls meiotic crossover frequency, we screened Arabidopsis accessions using fluorescent recombination reporters. We mapped a genetic modifier of crossover frequency in Col × Bur populations of Arabidopsis to a premature stop codon within TBP-ASSOCIATED FACTOR 4b (TAF4b), which encodes a subunit of the RNA polymerase II general transcription factor TFIID. The Arabidopsis taf4b mutation is a rare variant found in the British Isles, originating in South-West Ireland. Using genetics, genomics, and immunocytology, we demonstrate a genome-wide decrease in taf4b crossovers, with strongest reduction in the sub-telomeric regions. Using RNA sequencing (RNA-seq) from purified meiocytes, we show that TAF4b expression is meiocyte enriched, whereas its paralog TAF4 is broadly expressed. Consistent with the role of TFIID in promoting gene expression, RNA-seq of wild-type and taf4b meiocytes identified widespread transcriptional changes, including in genes that regulate the meiotic cell cycle and recombination. Therefore, TAF4b duplication is associated with acquisition of meiocyte-specific expression and promotion of germline transcription, which act directly or indirectly to elevate crossovers. This identifies a novel mode of meiotic recombination control via a general transcription factor.}, author = {Lawrence, Emma J. and Gao, Hongbo and Tock, Andrew J. and Lambing, Christophe and Blackwell, Alexander R. and Feng, Xiaoqi and Henderson, Ian R.}, issn = {0960-9822}, journal = {Current Biology}, keywords = {General Agricultural and Biological Sciences, General Biochemistry, Genetics and Molecular Biology}, number = {16}, pages = {2676--2686.e3}, publisher = {Elsevier BV}, title = {{Natural variation in TBP-ASSOCIATED FACTOR 4b controls meiotic crossover and germline transcription in Arabidopsis}}, doi = {10.1016/j.cub.2019.06.084}, volume = {29}, year = {2019}, } @article{12192, abstract = {Transposable elements (TEs), the movement of which can damage the genome, are epigenetically silenced in eukaryotes. Intriguingly, TEs are activated in the sperm companion cell – vegetative cell (VC) – of the flowering plant Arabidopsis thaliana. However, the extent and mechanism of this activation are unknown. Here we show that about 100 heterochromatic TEs are activated in VCs, mostly by DEMETER-catalyzed DNA demethylation. We further demonstrate that DEMETER access to some of these TEs is permitted by the natural depletion of linker histone H1 in VCs. Ectopically expressed H1 suppresses TEs in VCs by reducing DNA demethylation and via a methylation-independent mechanism. We demonstrate that H1 is required for heterochromatin condensation in plant cells and show that H1 overexpression creates heterochromatic foci in the VC progenitor cell. Taken together, our results demonstrate that the natural depletion of H1 during male gametogenesis facilitates DEMETER-directed DNA demethylation, heterochromatin relaxation, and TE activation.}, author = {He, Shengbo and Vickers, Martin and Zhang, Jingyi and Feng, Xiaoqi}, issn = {2050-084X}, journal = {eLife}, keywords = {General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, General Medicine, General Neuroscience}, publisher = {eLife Sciences Publications, Ltd}, title = {{Natural depletion of histone H1 in sex cells causes DNA demethylation, heterochromatin decondensation and transposon activation}}, doi = {10.7554/elife.42530}, volume = {8}, year = {2019}, } @article{10880, abstract = {Acquisition of evolutionary novelties is a fundamental process for adapting to the external environment and invading new niches and results in the diversification of life, which we can see in the world today. How such novel phenotypic traits are acquired in the course of evolution and are built up in developing embryos has been a central question in biology. Whole-genome duplication (WGD) is a process of genome doubling that supplies raw genetic materials and increases genome complexity. Recently, it has been gradually revealed that WGD and subsequent fate changes of duplicated genes can facilitate phenotypic evolution. Here, we review the current understanding of the relationship between WGD and the acquisition of evolutionary novelties. We show some examples of this link and discuss how WGD and subsequent duplicated genes can facilitate phenotypic evolution as well as when such genomic doubling can be advantageous for adaptation.}, author = {Yuuta, Moriyama and Koshiba-Takeuchi, Kazuko}, issn = {2041-2657}, journal = {Briefings in Functional Genomics}, keywords = {Genetics, Molecular Biology, Biochemistry, General Medicine}, number = {5}, pages = {329--338}, publisher = {Oxford University Press}, title = {{Significance of whole-genome duplications on the emergence of evolutionary novelties}}, doi = {10.1093/bfgp/ely007}, volume = {17}, year = {2018}, } @article{8436, abstract = {The exchange of metabolites between the mitochondrial matrix and the cytosol depends on β-barrel channels in the outer membrane and α-helical carrier proteins in the inner membrane. The essential translocase of the inner membrane (TIM) chaperones escort these proteins through the intermembrane space, but the structural and mechanistic details remain elusive. We have used an integrated structural biology approach to reveal the functional principle of TIM chaperones. Multiple clamp-like binding sites hold the mitochondrial membrane proteins in a translocation-competent elongated form, thus mimicking characteristics of co-translational membrane insertion. The bound preprotein undergoes conformational dynamics within the chaperone binding clefts, pointing to a multitude of dynamic local binding events. Mutations in these binding sites cause cell death or growth defects associated with impairment of carrier and β-barrel protein biogenesis. Our work reveals how a single mitochondrial “transfer-chaperone” system is able to guide α-helical and β-barrel membrane proteins in a “nascent chain-like” conformation through a ribosome-free compartment.}, author = {Weinhäupl, Katharina and Lindau, Caroline and Hessel, Audrey and Wang, Yong and Schütze, Conny and Jores, Tobias and Melchionda, Laura and Schönfisch, Birgit and Kalbacher, Hubert and Bersch, Beate and Rapaport, Doron and Brennich, Martha and Lindorff-Larsen, Kresten and Wiedemann, Nils and Schanda, Paul}, issn = {0092-8674}, journal = {Cell}, keywords = {General Biochemistry, Genetics and Molecular Biology}, number = {5}, pages = {1365--1379.e25}, publisher = {Elsevier}, title = {{Structural basis of membrane protein chaperoning through the mitochondrial intermembrane space}}, doi = {10.1016/j.cell.2018.10.039}, volume = {175}, year = {2018}, } @article{8438, author = {Kurauskas, Vilius and Hessel, Audrey and Dehez, François and Chipot, Christophe and Bersch, Beate and Schanda, Paul}, issn = {1545-9993}, journal = {Nature Structural & Molecular Biology}, keywords = {Molecular Biology, Structural Biology}, number = {9}, pages = {745--747}, publisher = {Springer Nature}, title = {{Dynamics and interactions of AAC3 in DPC are not functionally relevant}}, doi = {10.1038/s41594-018-0127-4}, volume = {25}, year = {2018}, } @article{8440, abstract = {Mycobacterium tuberculosis can remain dormant in the host, an ability that explains the failure of many current tuberculosis treatments. Recently, the natural products cyclomarin, ecumicin, and lassomycin have been shown to efficiently kill Mycobacterium tuberculosis persisters. Their target is the N-terminal domain of the hexameric AAA+ ATPase ClpC1, which recognizes, unfolds, and translocates protein substrates, such as proteins containing phosphorylated arginine residues, to the ClpP1P2 protease for degradation. Surprisingly, these antibiotics do not inhibit ClpC1 ATPase activity, and how they cause cell death is still unclear. Here, using NMR and small-angle X-ray scattering, we demonstrate that arginine-phosphate binding to the ClpC1 N-terminal domain induces millisecond dynamics. We show that these dynamics are caused by conformational changes and do not result from unfolding or oligomerization of this domain. Cyclomarin binding to this domain specifically blocked these N-terminal dynamics. On the basis of these results, we propose a mechanism of action involving cyclomarin-induced restriction of ClpC1 dynamics, which modulates the chaperone enzymatic activity leading eventually to cell death.}, author = {Weinhäupl, Katharina and Brennich, Martha and Kazmaier, Uli and Lelievre, Joel and Ballell, Lluis and Goldberg, Alfred and Schanda, Paul and Fraga, Hugo}, issn = {0021-9258}, journal = {Journal of Biological Chemistry}, keywords = {Cell Biology, Biochemistry, Molecular Biology}, number = {22}, pages = {8379--8393}, publisher = {American Society for Biochemistry & Molecular Biology}, title = {{The antibiotic cyclomarin blocks arginine-phosphate–induced millisecond dynamics in the N-terminal domain of ClpC1 from Mycobacterium tuberculosis}}, doi = {10.1074/jbc.ra118.002251}, volume = {293}, year = {2018}, } @article{13374, abstract = {Confining molecules to volumes only slightly larger than the molecules themselves can profoundly alter their properties. Molecular switches—entities that can be toggled between two or more forms upon exposure to an external stimulus—often require conformational freedom to isomerize. Therefore, placing these switches in confined spaces can render them non-operational. To preserve the switchability of these species under confinement, we work with a water-soluble coordination cage that is flexible enough to adapt its shape to the conformation of the encapsulated guest. We show that owing to its flexibility, the cage is not only capable of accommodating—and solubilizing in water—several light-responsive spiropyran-based molecular switches, but, more importantly, it also provides an environment suitable for the efficient, reversible photoisomerization of the bound guests. Our findings pave the way towards studying various molecular switching processes in confined environments.}, author = {Samanta, Dipak and Galaktionova, Daria and Gemen, Julius and Shimon, Linda J. W. and Diskin-Posner, Yael and Avram, Liat and Král, Petr and Klajn, Rafal}, issn = {2041-1723}, journal = {Nature Communications}, keywords = {General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary}, publisher = {Springer Nature}, title = {{Reversible chromism of spiropyran in the cavity of a flexible coordination cage}}, doi = {10.1038/s41467-017-02715-6}, volume = {9}, year = {2018}, } @article{14284, abstract = {Pore-forming toxins (PFT) are virulence factors that transform from soluble to membrane-bound states. The Yersinia YaxAB system represents a family of binary α-PFTs with orthologues in human, insect, and plant pathogens, with unknown structures. YaxAB was shown to be cytotoxic and likely involved in pathogenesis, though the molecular basis for its two-component lytic mechanism remains elusive. Here, we present crystal structures of YaxA and YaxB, together with a cryo-electron microscopy map of the YaxAB complex. Our structures reveal a pore predominantly composed of decamers of YaxA–YaxB heterodimers. Both subunits bear membrane-active moieties, but only YaxA is capable of binding to membranes by itself. YaxB can subsequently be recruited to membrane-associated YaxA and induced to present its lytic transmembrane helices. Pore formation can progress by further oligomerization of YaxA–YaxB dimers. Our results allow for a comparison between pore assemblies belonging to the wider ClyA-like family of α-PFTs, highlighting diverse pore architectures.}, author = {Bräuning, Bastian and Bertosin, Eva and Praetorius, Florian M and Ihling, Christian and Schatt, Alexandra and Adler, Agnes and Richter, Klaus and Sinz, Andrea and Dietz, Hendrik and Groll, Michael}, issn = {2041-1723}, journal = {Nature Communications}, keywords = {General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary}, publisher = {Springer Nature}, title = {{Structure and mechanism of the two-component α-helical pore-forming toxin YaxAB}}, doi = {10.1038/s41467-018-04139-2}, volume = {9}, year = {2018}, } @article{11065, abstract = {Premature aging disorders provide an opportunity to study the mechanisms that drive aging. In Hutchinson-Gilford progeria syndrome (HGPS), a mutant form of the nuclear scaffold protein lamin A distorts nuclei and sequesters nuclear proteins. We sought to investigate protein homeostasis in this disease. Here, we report a widespread increase in protein turnover in HGPS-derived cells compared to normal cells. We determine that global protein synthesis is elevated as a consequence of activated nucleoli and enhanced ribosome biogenesis in HGPS-derived fibroblasts. Depleting normal lamin A or inducing mutant lamin A expression are each sufficient to drive nucleolar expansion. We further show that nucleolar size correlates with donor age in primary fibroblasts derived from healthy individuals and that ribosomal RNA production increases with age, indicating that nucleolar size and activity can serve as aging biomarkers. While limiting ribosome biogenesis extends lifespan in several systems, we show that increased ribosome biogenesis and activity are a hallmark of premature aging.}, author = {Buchwalter, Abigail and HETZER, Martin W}, issn = {2041-1723}, journal = {Nature Communications}, keywords = {General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry}, publisher = {Springer Nature}, title = {{Nucleolar expansion and elevated protein translation in premature aging}}, doi = {10.1038/s41467-017-00322-z}, volume = {8}, year = {2017}, } @article{14005, abstract = {Strong-field photoelectron holography and laser-induced electron diffraction (LIED) are two powerful emerging methods for probing the ultrafast dynamics of molecules. However, both of them have remained restricted to static systems and to nuclear dynamics induced by strong-field ionization. Here we extend these promising methods to image purely electronic valence-shell dynamics in molecules using photoelectron holography. In the same experiment, we use LIED and photoelectron holography simultaneously, to observe coupled electronic-rotational dynamics taking place on similar timescales. These results offer perspectives for imaging ultrafast dynamics of molecules on femtosecond to attosecond timescales.}, author = {Walt, Samuel G. and Bhargava Ram, Niraghatam and Atala, Marcos and Shvetsov-Shilovski, Nikolay I and von Conta, Aaron and Baykusheva, Denitsa Rangelova and Lein, Manfred and Wörner, Hans Jakob}, issn = {2041-1723}, journal = {Nature Communications}, keywords = {General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary}, publisher = {Springer Nature}, title = {{Dynamics of valence-shell electrons and nuclei probed by strong-field holography and rescattering}}, doi = {10.1038/ncomms15651}, volume = {8}, year = {2017}, } @article{10370, abstract = {Eukaryotic cells are densely packed with macromolecular complexes and intertwining organelles, continually transported and reshaped. Intriguingly, organelles avoid clashing and entangling with each other in such limited space. Mitochondria form extensive networks constantly remodeled by fission and fusion. Here, we show that mitochondrial fission is triggered by mechanical forces. Mechano-stimulation of mitochondria – via encounter with motile intracellular pathogens, via external pressure applied by an atomic force microscope, or via cell migration across uneven microsurfaces – results in the recruitment of the mitochondrial fission machinery, and subsequent division. We propose that MFF, owing to affinity for narrow mitochondria, acts as a membrane-bound force sensor to recruit the fission machinery to mechanically strained sites. Thus, mitochondria adapt to the environment by sensing and responding to biomechanical cues. Our findings that mechanical triggers can be coupled to biochemical responses in membrane dynamics may explain how organelles orderly cohabit in the crowded cytoplasm.}, author = {Helle, Sebastian Carsten Johannes and Feng, Qian and Aebersold, Mathias J and Hirt, Luca and Grüter, Raphael R and Vahid, Afshin and Sirianni, Andrea and Mostowy, Serge and Snedeker, Jess G and Šarić, Anđela and Idema, Timon and Zambelli, Tomaso and Kornmann, Benoît}, issn = {2050-084X}, journal = {eLife}, keywords = {general immunology and microbiology, general biochemistry, genetics and molecular biology, general medicine, general neuroscience}, publisher = {eLife Sciences Publications}, title = {{Mechanical force induces mitochondrial fission}}, doi = {10.7554/elife.30292}, volume = {6}, year = {2017}, } @article{11072, abstract = {Spatiotemporal activation of RhoA and actomyosin contraction underpins cellular adhesion and division. Loss of cell–cell adhesion and chromosomal instability are cardinal events that drive tumour progression. Here, we show that p120-catenin (p120) not only controls cell–cell adhesion, but also acts as a critical regulator of cytokinesis. We find that p120 regulates actomyosin contractility through concomitant binding to RhoA and the centralspindlin component MKLP1, independent of cadherin association. In anaphase, p120 is enriched at the cleavage furrow where it binds MKLP1 to spatially control RhoA GTPase cycling. Binding of p120 to MKLP1 during cytokinesis depends on the N-terminal coiled-coil domain of p120 isoform 1A. Importantly, clinical data show that loss of p120 expression is a common event in breast cancer that strongly correlates with multinucleation and adverse patient survival. In summary, our study identifies p120 loss as a driver event of chromosomal instability in cancer. }, author = {van de Ven, Robert A.H. and de Groot, Jolien S. and Park, Danielle and van Domselaar, Robert and de Jong, Danielle and Szuhai, Karoly and van der Wall, Elsken and Rueda, Oscar M. and Ali, H. Raza and Caldas, Carlos and van Diest, Paul J. and HETZER, Martin W and Sahai, Erik and Derksen, Patrick W.B.}, issn = {2041-1723}, journal = {Nature Communications}, keywords = {General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry}, publisher = {Springer Nature}, title = {{p120-catenin prevents multinucleation through control of MKLP1-dependent RhoA activity during cytokinesis}}, doi = {10.1038/ncomms13874}, volume = {7}, year = {2016}, } @article{11073, abstract = {Human cancer cells bear complex chromosome rearrangements that can be potential drivers of cancer development. However, the molecular mechanisms underlying these rearrangements have been unclear. Zhang et al. use a new technique combining live-cell imaging and single-cell sequencing to demonstrate that chromosomes mis-segregated to micronuclei frequently undergo chromothripsis-like rearrangements in the subsequent cell cycle.}, author = {Hatch, Emily M. and HETZER, Martin W}, issn = {0092-8674}, journal = {Cell}, keywords = {General Biochemistry, Genetics and Molecular Biology}, number = {7}, pages = {1502--1504}, publisher = {Elsevier}, title = {{Linking micronuclei to chromosome fragmentation}}, doi = {10.1016/j.cell.2015.06.005}, volume = {161}, year = {2015}, } @article{11074, author = {Hatch, Emily M. and HETZER, Martin W}, issn = {0960-9822}, journal = {Current Biology}, keywords = {General Agricultural and Biological Sciences, General Biochemistry, Genetics and Molecular Biology}, number = {10}, pages = {PR397--R399}, publisher = {Elsevier}, title = {{Chromothripsis}}, doi = {10.1016/j.cub.2015.02.033}, volume = {25}, year = {2015}, }