Ajit P. Joglekar
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View article: Cell-APP: A generalizable method for cell annotation and cell-segmentation model training
Cell-APP: A generalizable method for cell annotation and cell-segmentation model training Open
Deep learning-based segmentation models can accelerate the analysis of high-throughput microscopy data by automatically identifying and classifying cells in images. However, the datasets needed to train these models are typically assembled…
View article: The structural flexibility of MAD1 facilitates the assembly of the Mitotic Checkpoint Complex
The structural flexibility of MAD1 facilitates the assembly of the Mitotic Checkpoint Complex Open
The spindle assembly checkpoint (SAC) safeguards the genome during cell division by generating an effector molecule known as the Mitotic Checkpoint Complex (MCC). The MCC comprises two subcomplexes: BUBR1:BUB3 and CDC20:MAD2, and the forma…
View article: BubR1 recruitment to the kinetochore via Bub1 enhances spindle assembly checkpoint signaling
BubR1 recruitment to the kinetochore via Bub1 enhances spindle assembly checkpoint signaling Open
Using quantitative cell biological observations and mathematical modeling, it is shown that BubR1 recruitment to the kinetochore via Bub1 promotes mitotic checkpoint complex generation, highlighting BubR1’s dual role of directly strengthen…
View article: The Structural Flexibility of MAD1 Facilitates the Assembly of the Mitotic Checkpoint Complex
The Structural Flexibility of MAD1 Facilitates the Assembly of the Mitotic Checkpoint Complex Open
The spindle assembly checkpoint (SAC) safeguards the genome during cell division by generating an effector molecule known as the Mitotic Checkpoint Complex (MCC). The MCC comprises two subcomplexes, and during its assembly, formation of th…
View article: Signaling protein abundance modulates the strength of the Spindle Assembly Checkpoint
Signaling protein abundance modulates the strength of the Spindle Assembly Checkpoint Open
Summary During mitosis, unattached kinetochores in a dividing cell signal to the Spindle Assembly Checkpoint to delay anaphase onset and prevent chromosome missegregation 1–4 . The signaling activity of these kinetochores and the likelihoo…
View article: Kre28–Spc105 interaction is essential for Spc105 loading at the kinetochore
Kre28–Spc105 interaction is essential for Spc105 loading at the kinetochore Open
Kinetochore (KTs) are macromolecular protein assemblies that attach sister chromatids to spindle microtubules (MTs) and mediate accurate chromosome segregation during mitosis. The outer KT consists of the KMN network, a protein super-compl…
View article: Kre28-Spc105 interaction is essential for Spc105 loading at the kinetochore
Kre28-Spc105 interaction is essential for Spc105 loading at the kinetochore Open
Kinetochores are macromolecular protein assemblies that attach sister chromatids to spindle microtubules and mediate accurate chromosome segregation during mit o sis. The outer kinetochore consists of the KMN network, a protein super-compl…
View article: BubR1 recruitment to the kinetochore via Bub1 enhances Spindle Assembly Checkpoint signaling
BubR1 recruitment to the kinetochore via Bub1 enhances Spindle Assembly Checkpoint signaling Open
During mitosis, unattached kinetochores in a dividing cell activate the Spindle Assembly Checkpoint (SAC) and delay anaphase onset by generating the anaphase-inhibitory Mitotic Checkpoint Complex (MCC). These kinetochores generate the MCC …
View article: Aurora B phosphorylates Bub1 to promote spindle assembly checkpoint signaling
Aurora B phosphorylates Bub1 to promote spindle assembly checkpoint signaling Open
Summary Accurate chromosome segregation during cell division requires amphitelic chromosome attachment to the spindle apparatus. It is ensured by the combined activity of the Spindle Assembly Checkpoint 1 (SAC), a signaling mechanism that …
View article: Adaptor Autoregulation Promotes Coordinated Binding within Clathrin Coats
Adaptor Autoregulation Promotes Coordinated Binding within Clathrin Coats Open
Membrane traffic is an essential process that allows protein and lipid exchange between the endocytic, lysosomal, and secretory compartments. Clathrin-mediated traffic between the trans-Golgi network and endosomes mediates responses to the…
View article: Vertebrate kinetochore protein architecture: protein copy number
Vertebrate kinetochore protein architecture: protein copy number Open
The stoichiometry of kinetochore components is determined, suggesting conservation between multiple microtubule-binding vertebrate and single microtubule-binding yeast kinetochores.To define the molecular architecture of the kinetochore in…
View article: Towards building a chromosome segregation machine
Towards building a chromosome segregation machine Open
All organisms, from bacteria to humans, face the daunting task of replicating, packaging and segregating up to two metres (about 6 × 109 base pairs) of DNA when each cell divides. This task is carried out up to a trillion times during the …
View article: Molecular architecture of a kinetochore–microtubule attachment site
Molecular architecture of a kinetochore–microtubule attachment site Open
Kinetochore attachment to spindle microtubule plus-ends is necessary for accurate chromosome segregation during cell division in all eukaryotes. The centromeric DNA of each chromosome is linked to microtubule plus-ends by eight structural-…
View article: Counting Kinetochore Protein Numbers in Budding Yeast Using Genetically Encoded Fluorescent Proteins
Counting Kinetochore Protein Numbers in Budding Yeast Using Genetically Encoded Fluorescent Proteins Open
Genetically encoded fluorescent proteins are an essential tool in cell biology, widely used for investigating cellular processes with molecular specificity. Direct uses of fluorescent proteins include studies of the in vivo cellular locali…
View article: Condensin Regulates the Stiffness of Vertebrate Centromeres
Condensin Regulates the Stiffness of Vertebrate Centromeres Open
When chromosomes are aligned and bioriented at metaphase, the elastic stretch of centromeric chromatin opposes pulling forces exerted on sister kinetochores by the mitotic spindle. Here we show that condensin ATPase activity is an importan…
View article: Chromosome Congression by Kinesin-5 Motor-Mediated Disassembly of Longer Kinetochore Microtubules
Chromosome Congression by Kinesin-5 Motor-Mediated Disassembly of Longer Kinetochore Microtubules Open
During mitosis, sister chromatids congress to the spindle equator and are subsequently segregated via attachment to dynamic kinetochore microtubule (kMT) plus-ends. A major question is how kMT plus-end assembly is spatially regulated to ac…
View article: Protein Architecture of the Human Kinetochore Microtubule Attachment Site
Protein Architecture of the Human Kinetochore Microtubule Attachment Site Open
Centromeric chromatin – spindle microtubule interactions mediated by kinetochores drive chromosome segregation. We have developed a two-color fluorescence light microscopy method that measures average label separation, Delta, at < 5 nm acc…
View article: A Sensitized Emission Based Calibration of FRET Efficiency for Probing the Architecture of Macromolecular Machines
A Sensitized Emission Based Calibration of FRET Efficiency for Probing the Architecture of Macromolecular Machines Open
Macromolecular machines participate in almost every cell biological function. These machines can take the form of well-defined protein structures such as the kinetochore, or more loosely organized protein assemblies like the endocytic coat…
View article: Mechanisms of force generation by end-on kinetochore-microtubule attachments
Mechanisms of force generation by end-on kinetochore-microtubule attachments Open
Generation of motile force is one of the main functions of the eukaryotic kinetochore during cell division. In recent years, the KMN network of proteins (Ndc80 complex, Mis12 complex and KNL-1 complex) has emerged as a highly conserved cor…
View article: In Vivo Protein Architecture of the Eukaryotic Kinetochore with Nanometer Scale Accuracy
In Vivo Protein Architecture of the Eukaryotic Kinetochore with Nanometer Scale Accuracy Open
The kinetochore is a macromolecular protein machine [1] that links centromeric chromatin to the plus-ends of one or more microtubules (MT), and segregates chromosomes during cell division. Its core structure consists of eight multi-compone…
View article: Pericentric Chromatin Is Organized into an Intramolecular Loop in Mitosis
Pericentric Chromatin Is Organized into an Intramolecular Loop in Mitosis Open
Cohesin proteins link sister chromatids and provide the basis for tension between bi-oriented sister chomatids in mitosis. Cohesin is concentrated at the centromere region of the chromosome despite the fact that sister centromeres can be s…
View article: Molecular architecture of the kinetochore-microtubule attachment site is conserved between point and regional centromeres
Molecular architecture of the kinetochore-microtubule attachment site is conserved between point and regional centromeres Open
Point and regional centromeres specify a unique site on each chromosome for kinetochore assembly. The point centromere in budding yeast is a unique 150-bp DNA sequence, which supports a kinetochore with only one microtubule attachment. In …
View article: The microtubule-based motor Kar3 and plus end–binding protein Bim1 provide structural support for the anaphase spindle
The microtubule-based motor Kar3 and plus end–binding protein Bim1 provide structural support for the anaphase spindle Open
In budding yeast, the mitotic spindle is comprised of 32 kinetochore microtubules (kMTs) and ∼8 interpolar MTs (ipMTs). Upon anaphase onset, kMTs shorten to the pole, whereas ipMTs increase in length. Overlapping MTs are responsible for th…
View article: Design Features of a Mitotic Spindle: Balancing Tension and Compression at a Single Microtubule Kinetochore Interface in Budding Yeast
Design Features of a Mitotic Spindle: Balancing Tension and Compression at a Single Microtubule Kinetochore Interface in Budding Yeast Open
Accurate segregation of duplicated chromosomes ensures that daughter cells get one and only one copy of each chromosome. Errors in chromosome segregation result in aneuploidy and have severe consequences on human health. Incorrect chromoso…
View article: The copy-number and varied strengths of MELT motifs in Spc105 balance the strength and responsiveness of the spindle assembly checkpoint
The copy-number and varied strengths of MELT motifs in Spc105 balance the strength and responsiveness of the spindle assembly checkpoint Open
During mitosis, the Spindle Assembly Checkpoint (SAC) maintains genome stability while also ensuring timely anaphase onset. To maintain genome stability, the SAC must be strong to delay anaphase even if just one chromosome is unattached, b…
View article: Author response: The copy-number and varied strengths of MELT motifs in Spc105 balance the strength and responsiveness of the spindle assembly checkpoint
Author response: The copy-number and varied strengths of MELT motifs in Spc105 balance the strength and responsiveness of the spindle assembly checkpoint Open
Article Figures and data Abstract Introduction Results Discussion Materials and methods Data availability References Decision letter Author response Article and author information Metrics Abstract During mitosis, the Spindle Assembly Check…
View article: Microtubule attachment and centromeric tension shape the protein architecture of the human kinetochore
Microtubule attachment and centromeric tension shape the protein architecture of the human kinetochore Open
Summary The nanoscale protein architecture of the kinetochore, a complex protein machine, plays an integral role in the molecular mechanisms underlying its functions in chromosome segregation. However, defining this architecture in human c…