Browsing by Author "Jana, Swadhin C"
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- Over-elongation of centrioles in cancer promotes centriole amplification and chromosome missegregationPublication . Marteil, Gaëlle; Guerrero, Adan; Vieira, André F; de Almeida, Bernardo P; Machado, Pedro; Mendonça, Susana; Mesquita, Marta; Villarreal, Beth; Fonseca, Irina; Francia, Maria E; Dores, Katharina; Martins, Nuno P; Jana, Swadhin C; Tranfield, Erin M; Barbosa-Morais, Nuno L; Paredes, Joana; Pellman, David; Godinho, Susana A; Bettencourt-Dias, MónicaCentrosomes are the major microtubule organising centres of animal cells. Deregulation in their number occurs in cancer and was shown to trigger tumorigenesis in mice. However, the incidence, consequence and origins of this abnormality are poorly understood. Here, we screened the NCI-60 panel of human cancer cell lines to systematically analyse centriole number and structure. Our screen shows that centriole amplification is widespread in cancer cell lines and highly prevalent in aggressive breast carcinomas. Moreover, we identify another recurrent feature of cancer cells: centriole size deregulation. Further experiments demonstrate that severe centriole over-elongation can promote amplification through both centriole fragmentation and ectopic procentriole formation. Furthermore, we show that overly long centrioles form over-active centrosomes that nucleate more microtubules, a known cause of invasiveness, and perturb chromosome segregation. Our screen establishes centriole amplification and size deregulation as recurrent features of cancer cells and identifies novel causes and consequences of those abnormalities.
- Rootletin organizes the ciliary rootlet to achieve neuron sensory function in DrosophilaPublication . Chen, Jieyan V; Kao, Ling-Rong; Jana, Swadhin C; Sivan-Loukianova, Elena; Mendonça, Susana; Cabrera, Oscar A; Singh, Priyanka; Cabernard, Clemens; Eberl, Daniel F; Bettencourt-Dias, Monica; Megraw, Timothy LCilia are essential for cell signaling and sensory perception. In many cell types, a cytoskeletal structure called the ciliary rootlet links the cilium to the cell body. Previous studies indicated that rootlets support the long-term stability of some cilia. Here we report that Drosophila melanogaster Rootletin (Root), the sole orthologue of the mammalian paralogs Rootletin and C-Nap1, assembles into rootlets of diverse lengths among sensory neuron subtypes. Root mutant neurons lack rootlets and have dramatically impaired sensory function, resulting in behavior defects associated with mechanosensation and chemosensation. Root is required for cohesion of basal bodies, but the cilium structure appears normal in Root mutant neurons. We show, however, that normal rootlet assembly requires centrioles. The N terminus of Root contains a conserved domain and is essential for Root function in vivo. Ectopically expressed Root resides at the base of mother centrioles in spermatocytes and localizes asymmetrically to mother centrosomes in neuroblasts, both requiring Bld10, a basal body protein with varied functions.
- A structural road map to unveil basal body composition and assemblyPublication . Jana, Swadhin C; Machado, Pedro; Bettencourt-Dias, MónicaThe Basal Body (BB) acts as the template for the axoneme, the microtubule‐basedstructure of cilia and flagella. Although several proteins were recently implicatedin both centriole and BB assembly and function, their molecular mechanisms are stillpoorly characterized. In this issue of The EMBO journal, Li and coworkersdescribe for the first time the near‐native structure of the BB at 33 Åresolution obtained by Cryo‐Electron Microscopy analysis of wild‐type (WT) isolatedChlamydomonas BBs. They identified several uncharacterized non‐tubulinstructures and variations along the length of the BB, which likely reflect thebinding and function of numerous macromolecular complexes. These complexes areexpected to define BB intrinsic properties, such as its characteristic structure andstability. Similarly to the high‐resolution structures of ribosome and nuclear porecomplexes, this study will undoubtedly contribute towards the future analysis ofcentriole and BB biogenesis, maintenance and function.