Article
Biochemistry & Molecular Biology
Babhrubahan Roy, Janice Sim, Simon J. Y. Han, Ajit P. Joglekar
Summary: The study investigates the interaction between Spc105 and Kre28 in budding yeast KTs. The results show that Spc105 and Kre28 localize at the KT with a 1:1 stoichiometry, and their interaction is important for Spc105 turnover and mutual recruitment at the KTs.
Article
Cell Biology
Wonkyung Oh, Ting Ting Wu, Seo-Yeon Jeong, Ho Jin You, Jung-Hee Lee
Summary: CtIP plays a critical role in regulating mitosis by interacting with TPX2 to control spindle dynamics and regulate the concentration of Aurora A and microtubule intensity at the spindle poles. Depletion of CtIP may lead to improper execution of mitosis and result in chromosomal instability.
Review
Cell Biology
Angela R. R. Bunning, Mohan L. L. Gupta Jr.
Summary: Accurate chromosome segregation is essential for cell and organismal viability. The mitotic spindle, composed mainly of dynamic microtubules, plays a crucial role in this process by forming a bipolar configuration and generating tension across sister kinetochores. Recent advances have shed light on the role of tension as a biophysical signal that ensures accurate chromosome segregation by destabilizing aberrant kinetochore-microtubule attachments and reinforcing correct connections.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Sara Carvalhal, Ingrid Bader, Martin A. Rooimans, Anneke B. Oostra, Jesper A. Balk, Rene G. Feichtinger, Christine Beichler, Michael R. Speicher, Johanna M. van Hagen, Quinten Waisfisz, Mieke van Haelst, Martijn Bruijn, Alexandra Tavares, Johannes A. Mayr, Rob M. F. Wolthuis, Raquel A. Oliveira, Job de Lange
Summary: BUB1 mutations cause neurodevelopmental disorder with cellular phenotypes similar to other syndromes.
Article
Biochemistry & Molecular Biology
Tobias Raisch, Giuseppe Ciossani, Ennio D'Amico, Verena Cmentowski, Sara Carmignani, Stefano Maffini, Felipe Merino, Sabine Wohlgemuth, Ingrid R. Vetter, Stefan Raunser, Andrea Musacchio
Summary: A high-resolution cryo-EM structure of the ROD-Zwilch-ZW10 complex reveals essential features, such as a farnesyl-binding site required for Spindly binding. In vitro assays demonstrate that the SAC kinase MPS1 is necessary and sufficient for corona assembly at supercritical concentrations of the RZZ-Spindly complex, and the molecular mechanism of phosphorylation-dependent filament nucleation is described.
Article
Biochemistry & Molecular Biology
Soumitra Polley, Helen Mueschenborn, Melina Terbeck, Anna De Antoni, Ingrid R. Vetter, Marileen Dogterom, Andrea Musacchio, Vladimir A. Volkov, Pim J. Huis In 't Veld
Summary: During cell division, the Ndc80 complex plays a crucial role in linking chromosomes to spindle microtubules. This study demonstrates that the Ndc80 loop promotes direct interactions between adjacent Ndc80 complexes, which are necessary for stable end-on kinetochore-microtubule attachment and spindle assembly checkpoint satisfaction. Mutations in the loop impair these interactions and lead to cell arrest in mitosis.
Article
Biochemistry & Molecular Biology
Aakanksha Sane, Shreyas Sridhar, Kaustuv Sanyal, Santanu K. Ghosh
Summary: Shugoshin proteins are evolutionarily conserved and play various roles in maintaining genomic stability in different cells, including regulating chromosome positioning, maintaining chromosomal separation efficiency, and serving as a component of the spindle assembly checkpoint to ensure cell stability. This study in Candida albicans reveals novel functions of Shugoshin, such as facilitating timely disassembly of the mitotic spindle and prolonging the response to improper kinetochore-microtubule attachments.
MOLECULAR MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Sikai Liu, Xiao Yuan, Ping Gui, Ran Liu, Olanrewaju Durojaye, Donald L. Hill, Chuanhai Fu, Xuebiao Yao, Zhen Dou, Xing Liu
Summary: In mitosis, the interaction between Cyclin B2 and Mad2 guides accurate chromosome segregation through their localization at the kinetochores.
Review
Cell Biology
Yuqing Zhang, Chunlin Song, Lei Wang, Hongfei Jiang, Yujing Zhai, Ying Wang, Jing Fang, Gang Zhang
Summary: This review summarizes the research progress on the role of Bub1 in mitosis over the past three decades. The studies have revealed that Bub1 plays important roles in checkpoint regulation and chromosome alignment. The essentiality of Bub1 in higher eukaryotic cells is discussed, along with some unresolved questions raised for future study.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Shelby L. McVey, Jenna K. Cosby, Natalie J. Nannas
Summary: Accurate segregation of chromosomes is crucial for the survival of organisms and cells, and tension plays a key role in this process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Wei Yue, Yue Wang, Tie-Gang Meng, Hong-Yong Zhang, Xin-Ran Zhang, Ying-Chun Ouyang, Yi Hou, Heide Schatten, Zhen-Bo Wang, Qing-Yuan Sun
Summary: This study investigates the role of outer kinetochore protein KNL1 in mouse oocytes and reveals its critical function in ensuring timely and accurate chromosome segregation during oocyte meiotic maturation.
Article
Biochemistry & Molecular Biology
Verena Cmentowski, Giuseppe Ciossani, Ennio d'Amico, Sabine Wohlgemuth, Mikito Owa, Brian Dynlacht, Andrea Musacchio
Summary: The RZZS complex and CENP-E are closely connected and reciprocally required for their own kinetochore recruitment and dynein localization to the corona.
Article
Cell Biology
Yanze Jian, Lingyun Nie, Sikai Liu, Yueyue Jiang, Zhen Dou, Xing Liu, Xuebiao Yao, Chuanhai Fu
Summary: The outer kinetochore acts as a platform for SAC initiation and mediating kinetochore-microtubule attachments. The inner kinetochore subcomplex CENP-S-CENP-X's involvement in regulating the SAC and kinetochore-microtubule attachments is not well characterized.
JOURNAL OF CELL SCIENCE
(2023)
Article
Developmental Biology
Marianne Roca, Lydia Besnardeau, Elisabeth Christians, Alex McDougall, Janet Chenevert, Stefania Castagnetti
Summary: The spindle assembly checkpoint (SAC) is responsible for delaying anaphase onset until all chromosomes are correctly attached to spindle microtubules, maintaining genome integrity. In chordate embryos, SAC is inactive or cell-cycle target machinery is unresponsive during early development, allowing mitotic progression despite spindle defects. However, in Phallusia mammillata embryos, the SAC delays mitotic progression from the 8th cleavage divisions and unattached kinetochores are recognized by the SAC machinery after the 7th cell cycle. The strength of SAC and its modulation by cell fate and size resemble SAC control in non-chordate embryos.
Article
Biochemistry & Molecular Biology
Nazario Bosco, Aleah Goldberg, Xin Zhao, Joseph C. Mays, Pan Cheng, Adam F. Johnson, Joy J. Bianchi, Cecilia Toscani, Elena Di Tommaso, Lizabeth Katsnelson, Dania Annuar, Sally Mei, Roni E. Faitelson, Ilan Y. Pesselev, Kareem S. Mohamed, Angela Mermerian, Elaine M. Camacho-Hernandez, Courtney A. Gionco, Julie Manikas, Yi-Shuan Tseng, Zhengxi Sun, Somayeh Fani, Sarah Keegan, Scott M. Lippman, David Fenyo, Simona Giunta, Stefano Santaguida, Teresa Davoli
Summary: We describe a system called KaryoCreate, which utilizes CRISPR-engineered technology to generate chromosome-specific aneuploidy. This is achieved by co-expression of an sgRNA targeting specific CENPA-binding alpha-satellite repeats and dCas9 fused to mutant KNL1. We successfully create gains or losses of targeted chromosomes in cellular progeny, with an average efficiency of 8% for gains and 12% for losses, validating this approach across 10 chromosomes.
Article
Oncology
Shan Wang, Xiaofang Huo, Yiping Yang, Yingxi Mo, Rahul K. Kollipara, Ralf Kittler
Summary: The deubiquitinase USP9X stabilizes EWS-FLI1 protein expression in Ewing sarcoma, and its inhibitor WP1130 can rapidly degrade EWS-FLI1 and inhibit the growth of Ewing sarcoma cells and tumors.
Article
Engineering, Biomedical
Gloria Ruiz-Gomez, Juliane Salbach-Hirsch, Jan-Niklas Duerig, Linda Koehler, Kanagasabai Balamurugan, Sandra Rother, Sophie-Luise Heidig, Stephanie Moeller, Matthias Schnabelrauch, Giulia Furesi, Sophie Paehlig, Pedro M. Guillem-Gloria, Christine Hofbauer, Vera Hintze, M. Teresa Pisabarro, Joerg Rademann, Lorenz C. Hofbauer
Summary: The WNT signaling pathway is important for bone development and regeneration, and abnormalities in WNT ligands and inhibitors are associated with various bone diseases. This study focused on glycosaminoglycan (GAG) recognition by DKK1, a WNT inhibitor, and aimed to develop WNT signaling regulators. Through a multidisciplinary approach, researchers designed and synthesized GAG derivatives with improved neutralizing properties for DKK1. These derivatives showed increased WNT pathway activity and improved bone regeneration in experimental models. The findings suggest that rationally engineered GAG variants could be used as novel therapeutic approaches.
Article
Oncology
Anne -Florence Blandin, Ross Giglio, Maya Srikanth Graham, Guadalupe Garcia, Seth Malinowski, Jared K. Woods, Shakti Ramkissoon, Lori Ramkissoon, Frank Dubois, Kathleen Schoolcraft, Jessica Tsai, Dayle Wang, Robert Jones, Jayne Vogelzang, Kristine Pelton, Sarah Becker, Fiona Watkinson, Claire Sinai, Elizabeth F. Cohen, Matthew A. Booker, Michael Y. Tolstorukov, Veerle Haemels, Liliana Goumnerova, Karen Wright, Mark Kieran, Katie Fehnel, David Reardon, Arnault Tauziede-Espariat, Rishi Lulla, Benjamin Carcamo, Stanley Chaleff, Alain Charest, Frederik De Smet, Azra H. Ligon, Adrian Dubuc, Melanie Pages, Pascale Varlet, Patrick Y. Wen, Brian M. Alexander, Susan Chi, Sanda Alexandrescu, Ralf Kittler, Robert Bachoo, Pratiti Bandopadhayay, Rameen Beroukhim, Keith L. Ligon
Summary: This study comprehensively analyzed ALK expression and genomic aberrations in 371 glioblastomas and validated the abnormalities in vitro and in vivo. The findings showed that ALK aberrations were present in 12% of gliomas across a wide age range and ALK fusions were more common in congenital/infant glioblastomas. ALK fusions promoted pathways related to tumor transformation and responded well to ALK inhibitors, supporting their use in clinical trials for glioblastomas in different age groups.
CLINICAL CANCER RESEARCH
(2023)
Article
Chemistry, Medicinal
Lydia Behring, Gloria Ruiz-Gomez, Christian Trapp, Maryann Morales, Robert Wodtke, Martin Koeckerling, Klaus Kopka, M. Teresa Pisabarro, Jens Pietzsch, Reik Loeser
Summary: The potential of designing irreversible alkyne-based inhibitors of cysteine cathepsins was explored by isoelectronic replacement in reversibly acting potent peptide nitriles. The synthesis of dipeptide alkynes and analogous nitriles was developed and investigated for their inhibition of cathepsins B, L, S, and K. Extensive structure-activity relationships were derived, and the selectivity profiles of alkynes do not necessarily reflect those of the nitriles. The inhibitory activity at the cellular level was demonstrated for selected compounds.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Plant Sciences
Paul Weiland, Felix Dempwolff, Wieland Steinchen, Sven-Andreas Freibert, Hui Tian, Timo Glatter, Roman Martin, Bart P. H. J. Thomma, Gert Bange, Florian Altegoer
Summary: Plant-pathogenic fungi play a major role in causing plant diseases and crop loss. In this study, the atomic structures of Cpl1 and Uvi2 proteins from Ustilago maydis and Ustilago hordei were determined. These proteins adopt a unique double-ψβ-barrel architecture and bind to chitin fragments in a novel mode. Cpl1 localizes to the cell wall of U. maydis and might coordinate with other cell wall-degrading and decorating proteins during maize infection. Deletion of uvi2 significantly impairs U. hordei virulence, indicating a diverging function from Cpl1.
MOLECULAR PLANT PATHOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Milica Jelicic, Lukas Theo Schmitt, Maciej Paszkowski-Rogacz, Angelika Walder, Nadja Schubert, Jenna Hoersten, Duran Sueruen, Frank Buchholz
Summary: This study develops a systematic computational workflow for annotating putative tyrosine-type site-specific recombinase (Y-SSR) systems and identifies and characterizes eight new naturally occurring Cre-type SSR systems. The activity of these systems is tested in bacterial and mammalian cells, and selectivity profiles are established for both new and established Cre-type SSRs. Potential pseudo-sites and off-targets for Y-SSRs in the human and mouse genome are also identified, providing valuable information for future genome surgery applications.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Maik Wolfram-Schauerte, Nadiia Pozhydaieva, Julia Grawenhoff, Luisa M. Welp, Ivan Silbern, Alexander Wulf, Franziska A. Billau, Timo Glatter, Henning Urlaub, Andres Jaeschke, Katharina Hoefer
Summary: Viral infections involve the use of ARTs to reprogram the host's genetic machinery, and this study shows that ModB can attach entire RNA chains to acceptor proteins in an 'RNAylation' reaction. ModB specifically attaches selected RNAs to ribosomal proteins, providing a mechanism for the phage to modulate the host's translation machinery. This work reveals a direct connection between RNA modification and post-translational protein modification.
Article
Multidisciplinary Sciences
Adrian Izquierdo-Martinez, Maria Billini, Vega Miguel-Ruano, Rogelio Hernandez-Tamayo, Pia Richter, Jacob Biboy, Maria T. Batuecas, Timo Glatter, Waldemar Vollmer, Peter L. Graumann, Juan A. Hermoso, Martin Thanbichler
Summary: This study demonstrates that a protein called DipM coordinates different peptidoglycan-remodeling pathways to regulate cell wall-degrading enzymes, ensuring proper cell constriction and daughter cell separation in bacteria.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Daniel Martin Klotz, Franziska Maria Schwarz, Anna Dubrovska, Kati Schuster, Mirko Theis, Alexander Krueger, Oliver Kutz, Theresa Link, Pauline Wimberger, Stephan Drukewitz, Frank Buchholz, Juergen Thomale, Jan Dominik Kuhlmann
Summary: We established an in vitro model for PARPi-resistant ovarian cancer and found that PARPi-resistant cells exhibit broad cross-resistance to other PARPis and chemotherapeutic drugs regardless of the BRCA1 status. Co-culture experiments showed that PARPi-resistant cells have a disadvantage in proliferation under drug-free conditions but quickly gain dominance under olaparib selection pressure, which can be blocked by ABC-transporter protein inhibitors. Overall, our well-characterized in vitro model is useful for dissecting mechanisms of PARPi resistance and studying the clonal dynamics of PARPi-resistant cells.
Article
Medicine, Research & Experimental
Samadrita Bhattacharyya, Rahul K. Kollipara, Gabriela Orquera-Tornakian, Sean Goetsch, Minzhe Zhang, Cameron Perry, Boxun Li, John M. Shelton, Minoti Bhakta, Jialei Duan, Yang Xie, Guanghua Xiao, Bret M. Evers, Gary C. Hon, Ralf Kittler, Nikhil V. Munshi
Summary: A comprehensive CCS-enriched CRE database named CCS-ATAC was established for studying CCS-wide and component-specific regulatory functions. CCS component-specific gene regulatory networks (GRNs) were constructed using transcription factor (TF) motifs, and specific TF sub-networks were identified and confirmed. CCS-ATAC was leveraged to improve annotation of existing human variants related to cardiac rhythm, and a potential dysregulated enhancer-target pair by a specific SNP was nominated.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Meeting Abstract
Oncology
Mia Hofstad, Lan Yu, Andrea Woods, Zoi Sychev, Collin Gilbreath, Xiaofang Huo, Ralf Kittler, Justin M. Drake, Ganesh V. Raj
Meeting Abstract
Oncology
Anne-Florence Blandin, Ross Giglio, Maya Srikanth Graham, Guadalupe Garcia, Seth Malinowski, Jared K. Woods, Shakti Ramkissoon, Lori Ramkissoon, Frank Dubois, Kate Schoolcraft, Jessica W. Tsai, Dayle K. Wang, Robert Jones, Jayne Vogelzang, Kristine Pelton, Sarah Becker, Fiona Watkinson, Claire Sinai, Elizabeth Cohen, Matthew Booker, Michael Tolstorukov, Veerle Haemels, Liliana Goumnerova, Karen Wright, Mark Kieran, Katie Fehnel, David Reardon, Arnault Tauziede-Espariat, Rishi Lulla, Benjamin Carcamo, Stanley Chaleff, Alain Charest, Frederik De Smet, Azra H. Ligon, Adrian Dubuc, Melanie Pages, Pascale Varlet, Patrick Wen, Brian Alexander, Susan Chi, Sanda Alexandrescu, Ralf Kittler, Robert Bachoo, Rameen Beroukhim, Pratiti Bandopadhayay, Keith L. Ligon
Article
Oncology
Kenneth E. Huffman, Long Shan Li, Ryan Carstens, Hyunsil Park, Luc Girard, Kimberley Avila, Shuguang Wei, Rahul Kollipara, Brenda Timmons, Jessica Sudderth, Nawal Bendris, Jiyeon Kim, Pamela Villalobos, Junya Fujimoto, Sandra Schmid, Ralph J. Deberardinis, Ignacio Wistuba, John Heymach, Ralf Kittler, Esra A. Akbay, Bruce Posner, Yuzhuo Wang, Stephen Lam, Steven A. Kliewer, David J. Mangelsdorf, John D. Minna
Summary: Glucocorticoid receptor (GR) is an important target for anti-cancer therapies in lymphoid cancers. This study finds that a dexamethasone-GR mediated anti-cancer response exists in a subset of aggressive non-small cell lung cancers (NSCLCs) with STK11/LKB1 mutations. The high expression of carbamoyl phosphate synthase 1 (CPS1) is strongly linked to LKB1 mutations and serves as a predictor of NSCLC dexamethasone sensitivity.
FRONTIERS IN ONCOLOGY
(2023)
Article
Biochemical Research Methods
Marco Herfurth, Franziska Mueller, Lotte Sogaard-Andersen, Timo Glatter
Summary: This protocol provides detailed instructions on how to identify stable and transient protein interactomes in bacteria using biotin ligase miniTurbo-based proximity labeling, including steps for control protein expression optimization, biotin labeling of bacteria, enrichment of biotinylated proteins, and sample processing for proteomic analysis.
Article
Biotechnology & Applied Microbiology
Lukas Theo Schmitt, Aksana Schneider, Jonas Posorski, Felix Lansing, Milica Jelicic, Manavi Jain, Shady Sayed, Frank Buchholz, Duran Sueruen
Summary: DEQSeq is a nanopore sequencing approach that enables the rational selection of favorable genome editing enzymes from directed molecular evolution experiments. It streamlines the process of identifying valuable variants for further study and application by capturing full-length sequences, editing efficiencies, and specificities from thousands of evolved enzymes simultaneously.