Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
13,250
result(s) for
"1966"
Sort by:
Chromosome biorientation produces hundreds of piconewtons at a metazoan kinetochore
High-fidelity transmission of the genome through cell division requires that all sister kinetochores bind to dynamic microtubules (MTs) from opposite spindle poles. The application of opposing forces to this bioriented configuration produces tension that stabilizes kinetochore–microtubule (kt–MT) attachments. Defining the magnitude of force that is applied to kinetochores is central to understanding the mechano-molecular underpinnings of chromosome segregation; however, existing kinetochore force measurements span orders of magnitude. Here we measure kinetochore forces by engineering two calibrated force sensors into the
Drosophila
kinetochore protein centromere protein (CENP)-C. Measurements of both reporters indicate that they are, on average, under ∼1–2 piconewtons (pNs) of force at metaphase. Based on estimates of the number of CENP-C molecules and MTs per
Drosophila
kinetochore and envisioning kinetochore linkages arranged such that they distribute forces across them, we propose that kinetochore fibres (k-fibres) exert hundreds of pNs of poleward-directed force to bioriented kinetochores.
Chromosomes bind microtubules (MT) from opposite spindle poles and the generated tension stabilizes kinetochore-MT attachments. Here the authors measure kinetochore forces by engineering two force sensors and propose that kinetochore fibers exert hundreds of pNs of force to bioriented kinetochores.
Journal Article
My Brother, My Land
A riveting and unapologetic account of Palestinian resistance, the story of one family's care for their land, and a reflection on love and heartache while living under military occupation. In 1967, Sireen Sawalha's mother, with her young children, walked back to Palestine against the traffic of exile. My Brother, My Land is the story of Sireen's family in the decades that followed and their lives in the Palestinian village of Kufr Ra'i. From Sireen's early life growing up in the shadow of the '67 War and her family's work as farmers caring for their land, to the involvement of her brother Iyad in armed resistance in the First and Second Intifada, Sami Hermez, with Sireen Sawalha, crafts a rich story of intertwining voices, mixing genres of oral history, memoir, and creative nonfiction. Through the lives of the Sawalha family, and the story of Iyad's involvement with the Palestinian Islamic Jihad, Hermez confronts readers with the politics and complexities of armed resistance and the ethical tensions and contradictions that arise, as well as with the dispossession and suffocation of people living under occupation and their ordinary lives in such times. Whether this story leaves readers discomforted, angry, or empowered, they will certainly emerge with a deeper understanding of the Palestinian predicament.
eBook
Structure of the human outer kinetochore KMN network complex
Faithful chromosome segregation requires robust, load-bearing attachments of chromosomes to the mitotic spindle, a function accomplished by large macromolecular complexes termed kinetochores. In most eukaryotes, the constitutive centromere-associated network (CCAN) complex of the inner kinetochore recruits to centromeres the ten-subunit outer kinetochore KMN network that comprises the KNL1C, MIS12C and NDC80C complexes. The KMN network directly attaches CCAN to microtubules through MIS12C and NDC80C. Here, we determined a high-resolution cryo-EM structure of the human KMN network. This showed an intricate and extensive assembly of KMN subunits, with the central MIS12C forming rigid interfaces with NDC80C and KNL1C, augmented by multiple peptidic inter-subunit connections. We also observed that unphosphorylated MIS12C exists in an auto-inhibited state that suppresses its capacity to interact with CCAN. Ser100 and Ser109 of the N-terminal segment of the MIS12C subunit Dsn1, two key targets of Aurora B kinase, directly stabilize this auto-inhibition. Our study indicates how selectively relieving this auto-inhibition through Ser100 and Ser109 phosphorylation might restrict outer kinetochore assembly to functional centromeres during cell division.
Here, the authors determine the structure of the human outer kinetochore KMN network complex, showing that it forms an extended and rigid rod-like structure and that it exists in an auto-inhibited state which can be relieved by phosphorylation.
Journal Article
Tension can directly suppress Aurora B kinase-triggered release of kinetochore-microtubule attachments
Chromosome segregation requires sister kinetochores to attach microtubules emanating from opposite spindle poles. Proper attachments come under tension and are stabilized, but defective attachments lacking tension are released, giving another chance for correct attachments to form. This error correction process depends on Aurora B kinase, which phosphorylates kinetochores to destabilize their microtubule attachments. However, the mechanism by which Aurora B distinguishes tense versus relaxed kinetochores remains unclear because it is difficult to detect kinase-triggered detachment and to manipulate kinetochore tension in vivo. To address these challenges, we apply an optical trapping-based assay using soluble Aurora B and reconstituted kinetochore-microtubule attachments. Strikingly, the tension on these attachments suppresses their Aurora B-triggered release, suggesting that tension-dependent changes in the conformation of kinetochores can regulate Aurora B activity or its outcome. Our work uncovers the basis for a key mechano-regulatory event that ensures accurate segregation and may inform studies of other mechanically regulated enzymes.
Tension stabilizes properly attached microtubules to kinetochores during chromosome segregation, and lack of tension leads to release. Here the authors show that tension directly suppresses Aurora B kinase mediated destabilization of reconstituted kinetochore-microtubule attachments, likely ensuring accurate chromosome segregation.
Journal Article
