A5073503402- Microtubule and mitosis dynamics
- Photosynthetic Processes and Mechanisms
- Protist diversity and phylogeny
- Chromosomal and Genetic Variations
- Genomics and Chromatin Dynamics
- Cellular transport and secretion
- Hemoglobin structure and function
- Plant nutrient uptake and metabolism
Max Planck Institute of Molecular Physiology
2021-2024
University of Duisburg-Essen
2022-2024
In metazoans, a ≈1 megadalton (MDa) multiprotein complex comprising the dynein-dynactin adaptor Spindly and ROD-Zwilch-ZW10 (RZZ) is building block of fibrous biopolymer, kinetochore corona. The corona assembles on mitotic kinetochores to promote microtubule capture spindle assembly checkpoint (SAC) signaling. We report here high-resolution cryo-EM structure that captures essential features RZZ complex, including farnesyl-binding site required for binding. Using highly predictive in vitro...
The centromere, a chromosome locus defined by the histone H3-like protein centromeric A (CENP-A), promotes assembly of kinetochore to bind microtubules during cell division. Centromere maintenance requires CENP-A be actively replenished dedicated machinery in early G
Cytoplasmic Dynein 1, or Dynein, is a microtubule minus end–directed motor. motility requires Dynactin and family of activating adaptors that stabilize the Dynein–Dynactin complex promote regulated interactions with cargo in space time. How limit activation to specialized subcellular locales unclear. Here, we reveal Spindly, mitotic adaptor at kinetochore corona, exists natively closed conformation occludes binding its CC1 box Spindly motif. A structure-based analysis identified various...
Chromosome biorientation on the mitotic spindle is prerequisite to errorless genome inheritance. CENP-E (kinesin-7) and dynein-dynactin (DD), microtubule motors with opposite polarity, promote from kinetochore corona, a polymeric structure whose assembly requires MPS1 kinase. The corona's building block consists of ROD, Zwilch, ZW10, DD adaptor Spindly (RZZS). How are scaffolded mutually coordinated in corona remains unclear. Here, we show that when prevented through inhibition, absolutely...
Abstract The centromere, a chromosome locus defined by the histone H3-like protein CENP-A, seeds kinetochore to bind microtubules during cell division. Centromere maintenance requires CENP-A be actively replenished dedicated machinery in early G1 cell-cycle phase, compensating for its two-fold dilution following DNA replication. Cyclin-dependent kinases (CDKs) limit deposition once per cycle and function as negative regulators outside G1. Antithetically, Polo-like kinase 1 (PLK1) promotes...
The spindle assembly checkpoint (SAC) makes mitotic exit contingent on completion of sister chromatid biorientation, but how this coordination is achieved in practice remains poorly understood. Kinetochores, megadalton chromosome attachment sites to microtubules, contribute SAC signaling. However, it unclear whether kinetochores are mere docking for proteins, or further co-orientation catalysts, including MAD1:MAD2 and BUB1:BUB3, facilitate Here, we combined biochemical reconstitutions the...
Cytoplasmic Dynein 1, or Dynein, is a microtubule minus-end directed motor. motility requires Dynactin and family of activating adaptors that stabilize the Dynein-Dynactin complex promote regulated interactions with cargo in space time. How limit activation to specialized subcellular locales unclear. Here, we reveal Spindly, mitotic adaptor at kinetochore corona, exists natively closed conformation occludes binding its CC1 box Spindly motif. A structure-based analysis identified various...
Chromosome biorientation on the mitotic spindle is prerequisite to errorless genome inheritance. CENP-E (kinesin 7) and Dynein-Dynactin (DD), microtubule motors with opposite polarity, promote from kinetochore corona, a polymeric structure whose assembly requires MPS1 kinase. The corona's building block consists of ROD, Zwilch, ZW10, DD adaptor Spindly (RZZS). How are scaffolded mutually coordinated in corona remains unclear. Here, we report near-complete depletion RZZS kinetochores after...
In metazoans, a ≍1 megadalton (MDa) super-complex comprising the Dynein-Dynactin adaptor Spindly and ROD-Zwilch-ZW10 (RZZ) complex is building block of fibrous biopolymer, kinetochore corona. The corona assembles on mitotic kinetochores to promote microtubule capture spindle assembly checkpoint (SAC) signaling. We report here high-resolution cryo-EM structure that captures essential features RZZ complex, including farnesyl binding site required for binding. Using highly predictive in vitro...