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
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
Andrew R. Popchock, Joshua D. Larson, Julien Dubrulle, Charles L. Asbury, Sue Biggins
Summary: Eukaryotic chromosome segregation requires a large machine called the kinetochore, which contains CENP-A and is responsible for nucleosome formation. This study investigates the functions of the chaperone protein HJURP in CENP-A deposition and the conservation of high AT DNA content at centromeres. Through a microscopy assay, it is found that CENP-A can arrive at centromeres without HJURP but stable incorporation requires HJURP and other DNA-binding proteins. Homopolymer AT runs in yeast centromeres are also essential for efficient CENP-A deposition. These findings provide insights into nucleosome formation and lay the foundation for future studies on kinetochore complexes.
Article
Biochemistry & Molecular Biology
Laura Tovini, Sarah C. Johnson, Molly A. Guscott, Alexander M. Andersen, Diana Carolina Johanna Spierings, Rene Wardenaar, Floris Foijer, Sarah E. McClelland
Summary: Cancer cells exhibit persistent chromosomal instability, with different tumor types showing characteristic subsets of aneuploidies. Researchers used dCas9 as a carrier to recruit the kinetochore-nucleating domain of CENP-T protein to ectopically assemble kinetochores near specific genomic loci, resulting in increased chromosome instability and partial aneuploidies of target chromosomes in various cell types. The study also analyzed potential endogenous repeats that could support ectopic kinetochore formation.
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
Immunology
Lorenzo Brusini, Simon D'Archivio, Jennifer McDonald, Bill Wickstead
Summary: Kinetochores play a crucial role in eukaryotes, binding chromosomes to the mitotic spindle. While the composition of kinetochores varies greatly among extant eukaryotes, a stable 9-protein kinetoplastid outer kinetochore complex has been identified in trypanosomes. This complex incorporates proteins from other nuclear processes and bridges inner- and outer-kinetochore components, suggesting design parallels in organisms with diverse kinetochore composition.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Cell Biology
Janet K. Jang, Amy C. Gladstein, Arunika Das, Joanatta G. Shapiro, Zachary L. Sisco, Kim S. McKim
Summary: The study highlights the critical role of PP2A in maintaining spindle assembly and sister chromatid cohesion in Drosophila oocytes, showing an interplay with Aurora B activity.
JOURNAL OF CELL SCIENCE
(2021)
Article
Cell Biology
Rachel L. Flores, Zachary E. Peterson, Alex Zelter, Michael Riffle, Charles L. Asbury, Trisha N. Davis
Summary: The study reveals that interactions between Ndc80 complex and Dam1 complex through three distinct interacting regions play a vital role in supporting both short-term and long-term tip-coupling during mitosis. Phosphorylation by Aurora B kinase may modulate these interactions and impact the accuracy of mitosis.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Biology
Nicolas Macaisne, Laura Bellutti, Kimberley Laband, Frances Edwards, Laras Pitayu-Nugroho, Alison Gervais, Thadshagine Ganeswaran, Helene Geoffroy, Gilliane Maton, Julie C. Canman, Benjamin Lacroix, Julien Dumont
Summary: During cell division, the microtubule-based spindle plays a crucial role in chromosome segregation. The interaction between spindle microtubules and kinetochores is essential for the proper alignment and segregation of chromosomes. This study focuses on a kinetochore module called the BHC module, which consists of BUB-1, HCP-1/2, and CLS-2, and shows that it stabilizes microtubules, promoting spindle formation and accurate chromosome segregation.
Article
Multidisciplinary Sciences
Klara Plackova, Petr Bures, Frantisek Zedek
Summary: The study found that genome size is a strong predictor of total centromere size in Eukaryotes, regardless of phylogenetic relatedness and centromere type. This implies a common mechanism maintaining stable total centromere size across Eukaryotes.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Kim S. McKim
Summary: The chromosome passenger complex (CPC) plays a crucial role in spindle assembly and error correction by interacting with chromatin and microtubules. These dual interactions enhance CPC concentration for efficient kinase activity and responsiveness to specific conditions in the cell. CPC-microtubule interactions are vital for processes such as meiotic division and metaphase I error correction.
Review
Biochemistry & Molecular Biology
Taekyung Kim
Summary: This review summarizes the recent literature on the kinetochore recruitment mechanisms of PLK1 and its roles in spindle assembly checkpoint and attachment between kinetochores and spindle microtubules, providing an overview of how the local distribution of PLK1 could regulate major pathways in mitosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Marin Barisic, Girish Rajendraprasad
Summary: Recent research has shown that in human cells, the continuous poleward motion of microtubules in mitotic spindles is driven by four mitotic kinesins, with specific contributions at different stages of mitosis. While the molecular mechanism behind this cellular phenomenon has been elucidated, the functional roles of microtubule poleward flux during cell division remain largely unknown.
Article
Biochemistry & Molecular Biology
Jacob A. Zahm, Simon Jenni, Stephen C. Harrison
Summary: The Ndc80 kinetochore complex connects mitotic spindle microtubules and centromere-associated proteins. AlphaFold 2 (AF2) was used to predict the structure of the Ndc80 'loop' and the Ndc80 : Nuf2 globular head domains. The predictions guided the design of crystallizable constructs, which closely matched the predicted structures. The structural results provide insights into the molecular model of the kinetochore-microtubule interface and the stabilization of kinetochore attachments.
Review
Cell Biology
J. Richard McIntosh
Summary: Anaphase A refers to the movement of recently separated chromosomes to the spindle pole they face, accompanied by the shortening of kinetochore-attached microtubules. Cells regulate microtubule dynamics by localizing relevant enzymes and microtubule-associated proteins to specific places, while motor enzymes contribute to anaphase A by altering microtubule stability and pushing or pulling microtubules through the cell.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Abigail R. Gerhold, Joel Ryan, Julie-Nathalie Vallee-Trudeau, Jonas F. Dorn, Jean-Claude Labbe, Paul S. Maddox
Article
Cell Biology
Anne-Marie Ladouceur, Jonas F. Dorn, Paul S. Maddox
JOURNAL OF CELL BIOLOGY
(2015)
Article
Cell Biology
Stephanie Duhamel, Charlotte Girondel, Jonas F. Dorn, Pierre-Luc Tanguay, Laure Voisin, Ron Smits, Paul S. Maddox, Sylvain Meloche
Article
Computer Science, Cybernetics
Cecily Morrison, Kit Huckvale, Bob Corish, Jonas Dorn, Peter Kontschieder, Kenton O'Hara, Frank Dahlke, Ludwig Kappos, Bernard Uitdehaag, Jessica Burggraaff, Christian Kamm, Saskia Steinheimer, Marcus D'Souza, Antonio Criminisi, Abigail Sellen
HUMAN-COMPUTER INTERACTION
(2016)
Article
Cell Biology
Jonas F. Dorn, Li Zhang, Tan-Trao Phi, Benjamin Lacroix, Paul S. Maddox, Jian Liu, Amy Shaub Maddox
MOLECULAR BIOLOGY OF THE CELL
(2016)
Review
Behavioral Sciences
Katrin Parmar, Christine Stadelmann, Maria A. Rocca, Dawn Langdon, Egidio D'Angelo, Marcus D'Souza, Jessica Burggraaff, Christiane Wegner, Jaume Sastre-Garriga, Alonso Barrantes-Freer, Jonas Dorn, Bernard M. J. Uitdehaag, Xavier Montalban, Jens Wuerfel, Christian Enzinger, Alex Rovira, Mar Tintore, Massimo Filippi, Ludwig Kappos, Till Sprenger
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2018)
Article
Clinical Neurology
Caspar E. P. van Munster, Marcus D'Souza, Saskia Steinheimer, Christian P. Kamm, Jessica Burggraaff, Manuela Diederich, Kristina Kravalis, Jonas Dorn, Lorcan Walsh, Frank Dahlke, Ludwig Kappos, Bernard M. J. Uitdehaag
MULTIPLE SCLEROSIS JOURNAL
(2019)
Article
Rehabilitation
Saskia Steinheimer, Jonas F. Dorn, Cecily Morrison, Advait Sarkar, Marcus D'Souza, Jacques Boisvert, Rishi Bedi, Jessica Burggraaff, Peter Kontschieder, Frank Dahlke, Abigail Sellen, Bernard M. J. Uitdehaag, Ludwig Kappos, Christian P. Kamm
DISABILITY AND REHABILITATION
(2020)
Article
Rehabilitation
Jessica Burggraaff, Jonas Dorn, Marcus D'Souza, Cecily Morrison, Christian P. Kamm, Peter Kontschieder, Prejaas Tewarie, Saskia Steinheimer, Abigail Sellen, Frank Dahlke, Ludwig Kappos, Bernard Uitdehaag
ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
(2020)
Article
Health Care Sciences & Services
Marcus D'Souza, Caspar E. P. Van Munster, Jonas F. Dorn, Alexis Dorier, Christian P. Kamm, Saskia Steinheimer, Frank Dahlke, Bernard M. J. Uitdehaag, Ludwig Kappos, Matthew Johnson
JOURNAL OF MEDICAL INTERNET RESEARCH
(2020)
Article
Mathematical & Computational Biology
Mark Baillie, Conor Moloney, Carsten Philipp Mueller, Jonas Dorn, Janice Branson, David Ohlssen
Summary: There is a growing interest in the application of data science in the pharmaceutical industry, as it brings new perspectives, methods, and skill sets to answer fundamental questions in drug development. However, there are obstacles to overcome, such as defining data science, its relationship with existing fields, and identifying best practices. This article covers these themes and proposes a definition and framework for good data science practice in the context of drug development.
STATISTICS IN BIOPHARMACEUTICAL RESEARCH
(2023)
Article
Health Care Sciences & Services
Alison Keogh, Jonas F. Dorn, Lorcan Walsh, Francesc Calvo, Brian Caulfield
JMIR MHEALTH AND UHEALTH
(2020)
Proceedings Paper
Computer Science, Artificial Intelligence
Niladri Sett, Brian Mac Namee, Francesc Calvo, Brian Caulfield, John Costello, Seamas C. Donnelly, Jonas F. Dorn, Louis Jeay, Alison Keogh, Killian McManus, Ronan H. Mullan, Emer O'Hare, Caroline G. M. Perraudin
ARTIFICIAL INTELLIGENCE XXXVI
(2019)
Article
Computer Science, Artificial Intelligence
Cecily Morrison, Kit Huckvale, Bob Corish, Richard Banks, Martin Grayson, Jonas Dorn, Abigail Sellen, Sian Lindley
ACM TRANSACTIONS ON INTERACTIVE INTELLIGENT SYSTEMS
(2018)
Proceedings Paper
Computer Science, Artificial Intelligence
Peter Kontschieder, Jonas F. Dorn, Cecily Morrison, Robert Corish, Darko Zikic, Abigail Sellen, Marcus D'Souza, Christian P. Kamm, Jessica Burggraaff, Prejaas Tewarie, Thomas Vogel, Michela Azzarito, Ben Glocker, Peter Chin, Frank Dahlke, Chris Polman, Ludwig Kappos, Bernard Uitdehaag, Antonio Criminisi
MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI 2014, PT II
(2014)