
Cell Cycle Regulation
Mónica Bettencourt-Dias
The Cell Cycle Regulation laboratory is interested in general principles of biology concerning the assembly and maintenance of complex subcellular structures, as well as their variations, which can occur during development, disease and evolution. Researchers use complex cytoskeletal assemblies, such as centrioles and cilia, as study subjects.
Centrioles are microtubule-based cylinders that form centrosomes and cilia, structures involved in many functions, from cell division to motility. Centrosome defects are seen in many cancers, while abnormalities in cilia lead to many diseases including polycystic kidneys and infertility.
Finally, centrioles and cilia are highly conserved throughout the eukaryotic tree of life, but have been lost in a variety of species, being an excellent study case to research the evolution of eukaryotic cellular structures.
Using multidisciplinary approaches the laboratory identified critical mechanisms regulating centriole and cilia assembly, maintenance and function. They have also characterized the mechanisms involved in the variation of those structures during development and evolution, and in human disease.
Funding Member
Publications
- Sónia Gomes Pereira, Ana Laura Sousa, Catarina Nabais, Tiago Paixão, Alexander J.Holmes, Martin Schorb, Gohta Goshima, Erin M. Tranfield, Jörg D. Becker, Mónica Bettencourt-Dias (2021) The 3D architecture and molecular foundations of de novo centriole assembly via bicentrioles. Current Biology
- Nabais C., Pessoa D., de-Carvalho J.,van Zanten T., Duarte P., Mayor S., Carneiro J., Telley I.A., Bettencourt-Dias M. (2021) Plk4 triggers autonomous de novo centriole biogenesis and maturation. J Cell Biol 220 (5):e202008090
- Peneda C, Lopes CAM, Bettencourt-Dias M. (2020) Studying Centriole Duplication and Elongation in Human Cells. Methods Mol Biol. 2101: 147-162
- Ito D, Zitouni S, Jana SC, Duarte P, Surkont J, Carvalho-Santos Z, Pereira-Leal JB, Ferreira MG, Bettencourt-Dias M. (2019) Pericentrin-mediated SAS-6 recruitment promotes centriole assembly. eLife 8
- Gouveia SM, Zitouni S, Kong D, Duarte P, Gomes BF, Sousa AL, Tranfield EM, Hyman A, Loncarek J, Bettencourt-Dias M. (2018) PLK4 is a microtubule-associated protein that self assembles promoting de novo MTOC formation. J Cell Sci. 132(4)
- Jana SW, Mendonça S, Machado P, Werner S, Rocha J, Pereira A, Maiato H, Bettencourt-Dias M. (2018) Differential Regulation of Transition Zone and Centriole Proteins Contributes to Ciliary Base Diversity. Nature Cell Biology 20(8):928-941
- Lopes, C.A.M., M. Mesquita, A.I. Cunha, J. Cardoso, S. Carapeta, C. Laranjeira, A.E. Pinto, J.B. Pereira-Leal, A. Dias-Pereira, M. Bettencourt-Dias, and P. Chaves (2018) Centrosome amplification arises before neoplasia and increases upon p53 loss in tumorigenesis. J Cell Biol 217(7):2353-2363
- Marteil, G., A. Guerrero, A.F. Vieira, B.P. de Almeida, P. Machado, S. Mendonca, M. Mesquita, B. Villarreal, I.Fonseca, M.E. Francia, K. Dores, N.P. Martins, S.C. Jana, E.M. Tranfield, N.L. Barbosa-Morais, J. Paredes, D. Pellman, S.A. Godinho, and M. Bettencourt- Dias (2018) Over-elongation of centrioles in cancer promotes centriole amplification and chromosome missegregation. Nat Commun 9(1):1258
- Pimenta-Marques, A., Bento, I., Lopes, C.A., Duarte, P., Jana, S.C., Bettencourt-Dias, M. (2016) A mechanism for the elimination of the female gamete centrosome in Drosophila melanogaster.. Science. 353(6294):aaf4866
- Zitouni, S., Francia, M.E., Leal, F., Montenegro-Gouveia, S., Nabais, C., Duarte, P., Gilberto, S., Brito, D., Moyer, T., Kandels-Lewis, S., Ohta, M., Kitagawa, D., Holland, A.J., Karsenti, E., Lorca, T., Lince-Faria, M., Bettencourt-Dias, M. (2016) CDK1 prevents unscheduled PLK4-STIL complex assembly in centriole biogenesis.. Curr Biol. 26(9):1127-37
- Lopes, C.A., Jana, S.C., Cunha-Ferreira, I., Bento, I., Zitouni, Z., Duarte, P., Gilberto, S., Guerrero, A., Lince-Faria, M., Carneiro, J., Bettencourt-Dias, M. (2015) PLK4 trans-autoactivation controls centriole biogenesis in space.. Dev Cell. 35(2):222-35
- Jana, S.C.*, Marteil, G.*, Bettencourt-Dias, M. (2014) Mapping molecules to structure: unveiling secrets of centriole and cilia assembly with near-atomic resolution.. Curr Opin Cell Biol. 26:96-106
- Zitouni, S., Nabais, C., Jana, S.C., Guerrero, A., Bettencourt-Dias, M. (2014) Polo-like kinases: structural variations lead to multiple functions.. Nat Rev Mol Cell Biol. 15(7):433-52
- Cunha-Ferreira, I., Bento, I., Pimenta-Marques, A., Jana, S.C., Lince-Faria, M., Duarte, P., Borrego-Pinto, J., Gilberto, S., Amado, T., Brito, D., Rodrigues-Martins, A., Debski, J. Dzhindzhev, N., Bettencourt-Dias, M. (2013) Regulation of auto-phosphorylation controls PLK4 self-destruction and centriole number.. Curr Biol. 23(22):2245-54
- Carvalho-Santos, Z., Machado, P., Alvarez-Martins, I., Gouveia, S., Duarte, P., Amado, T., Jana, S.C., Branco, P., Freitas, M., Silva, S., Antony, C., Bandeiras, T., Bettencourt-Dias, M. (2012) BLD10/CEP135 is a microtubule-associated protein that controls the formation of the flagellum central microtubule pair.. Dev Cell. 23 (2):412-24
- Carvalho-Santos, Z., Azimzadeh, J., Pereira-Leal, J.B., Bettencourt-Dias, M. (2011) Evolution: Tracing the origins of centrioles, cilia, and flagella.. J Cell Biol. 194(2):165-75
- Dzhindzhev, N.S., Yu, Q.D., Weiskopf, K., Tzolovsky, G., Cunha-Ferreira, I., Riparbelli, M., Rodrigues-Martins, A., Bettencourt-Dias, M. , Callaini, G., Glover, D.M. (2010) Asterless is a scaffold for the onset of centriole assembly.. Nature. 467(7316):714-8
- Carvalho-Santos, Z., Machado, P., Branco, P., Cadete, F., Rodrigues-Martins, A., Pereira-Leal, J.B., Bettencourt-Dias, M. (2010) Stepwise evolution of centriole assembly.. J Cell Sci. 123(Pt 9):1414-26