Where Ideas Grow

Chromosome Instability & Dynamics

ABOUT

Mitosis is the process by which the nuclear material is divided and transmitted to the next generation of cells in eukaryotic organisms. It is not only an essential process for life, but mitotic abnormalities have also been related with aneuploidy and chromosomal instability observed in many human cancers. Aneuploidy is also the basis of many birth defects and the main cause of spontaneous abortions in humans. Clearly, elucidating the molecular mechanisms behind chromosome segregation fidelity will have broad biological significance, while contributing to unveil the routes of aneuploidy and their implications to human health/disease. The major goal of our laboratory is to understand how chromosome segregation is regulated in time and space and how mitotic failure may lead to aneuploidy, contributing to a better understanding of how cancer arises and how it could be treated. Currently, we are investigating the role of the tubulin code in mitosis and the mechanisms that regulate the anaphase-telophase transition in mammals.

 

RESEARCH

Our group is interested in the spatial and temporal control mechanisms that ensure the fidelity of chromosome segregation. Over the last five years, our team has uncovered the role of chromosomal forces in determining mitotic spindle architecture and the implications for mitotic spindle multipolarity without centrosome amplification (Logarinho et al., Nat  Cell Biol, 2012; Maiato and Logarinho, Nat Cell Biol, 2014). More recently, we established the mechanism of peripheral chromosome alignment to the cell’s equator involving the coordinated activities of motor proteins at kinetochores and chromosome arms (Barisic et al., Nat Cell Biol, 2014) and the recognition of tubulin detyrosination by CENP-E (Barisic et al., Science, 2015). We have also completed a genome-wide screen for acentrosomal spindle assembly in animal somatic cells (Moutinho-Pereira et al., PNAS, 2013), demonstrating a constitutive centrosome-independent spindle assembly program and how this program adapts to the presence/absence of centrosomes in animal somatic cells. Lastly, we have uncovered a new mitotic checkpoint that delays chromosome decondensation and completion of nuclear envelope reassembly until effective separation of sister chromatids during anaphase is achieved (Afonso et al., Science, 2014).

 

Drosophila S2 cell undergoing mitosis. The mitotic spindle is in yellow and chromosomes are in blue. (Credits: Sara Moutinho Pereira/CID Lab)

Team

Selected Publications

Ferreira L.T., Orr B., Rajendraprasad G., Pereira A.J., Lemos C., Lima J.T., Boldú C.G., Ferreira J.G., Barisic M., Maiato H.,
ARTICLE a-Tubulin detyrosination impairs mitotic error correction by suppressing MCAK centromeric activity. Journal of Cell Biology219(4):, 2020. [Journal: Article] [CI: 12] [IF: 10,5]
DOI: 10.1083/JCB.201910064 SCOPUS: 85084031422

Girão H., Okada N., Rodrigues T.A., Silva A.O., Figueiredo A.C., Garcia Z., Moutinho-Santos T., Hayashi I., Azevedo J.E., Macedo-Ribeiro S., Maiato H.,
CLASP2 binding to curved microtubule tips promotes flux and stabilizes kinetochore attachments. Journal of Cell Biology219(2):, 2020. [Journal: Article] [CI: 10] [IF: 10,5]
DOI: 10.1083/jcb.201905080 SCOPUS: 85076332070

Pereira A., Sousa M., Almeida A.C., Ferreira L.T., Costa A.R., Novais-Cruz M., Ferrás C., Sousa M.M., Sampaio P., Belsley M., Maiato H.,
Coherent-hybrid STED: High contrast subdiffraction imaging using a bi-vortex depletion beam. Optics Express27(6):8092-8111, 2019. [Journal: Article] [CI: 16] [IF: 3,7]
DOI: 10.1364/OE.27.008092 SCOPUS: 85063447164

Afonso O., Castellani C.M., Cheeseman L.P., Ferreira J.G., Orr B., Ferreira L.T., Chambers J.J., Morais-De-Sá E., Maresca T.J., Maiato H.,
Spatiotemporal control of mitotic exit during anaphase by an aurora B-Cdk1 crosstalk. eLife8:, 2019. [Journal: Article] [CI: 20] [IF: 7,1]
DOI: 10.7554/eLife.47646 SCOPUS: 85071529547

Drpic D., Almeida A.C., Aguiar P., Renda F., Damas J., Lewin H.A., Larkin D.M., Khodjakov A., Maiato H.,
Chromosome Segregation Is Biased by Kinetochore Size. Current Biology28(9):1344-1356.e5, 2018. [Journal: Article] [CI: 42] [IF: 9,2]
DOI: 10.1016/j.cub.2018.03.023 SCOPUS: 85045880247

Barisic M., Silva E Sousa R., Tripathy S.K., Magiera M.M., Zaytsev A.V., Pereira A.L., Janke C., Grishchuk E.L., Maiato H.,
Microtubule detyrosination guides chromosomes during mitosis. Science348(6236):799-803, 2015. [Journal: Article] [CI: 138] [IF: 34,7]
DOI: 10.1126/science.aaa5175 SCOPUS: 84929340886

Barisic M., Aguiar P., Geley S., Maiato H.,
Kinetochore motors drive congression of peripheral polar chromosomes by overcoming random arm-ejection forces. Nature Cell Biology16(12):1249-1256, 2014. [Journal: Article] [CI: 86] [IF: 19,7]
DOI: 10.1038/ncb3060 SCOPUS: 84925285786

Afonso O., Matos I., Pereira A.J., Aguiar P., Lampson M.A., Maiato H.,
Feedback control of chromosome separation by a midzone Aurora B gradient. Science345(6194):332-336, 2014. [Journal: Article] [CI: 76] [IF: 33,6]
DOI: 10.1126/science.1251121 SCOPUS: 84904382634

Maiato H., Logarinho E.,
Mitotic spindle multipolarity without centrosome amplification. Nature Cell Biology16(5):386-394, 2014. [Journal: Review] [CI: 97] [IF: 19,7]
DOI: 10.1038/ncb2958 SCOPUS: 84899790283

Logarinho E., Maffini S., Barisic M., Marques A., Toso A., Meraldi P., Maiato H.,
CLASPs prevent irreversible multipolarity by ensuring spindle-pole resistance to traction forces during chromosome alignment. Nature Cell Biology14(3):295-303, 2012. [Journal: Article] [CI: 64] [IF: 20,8]
DOI: 10.1038/ncb2423 SCOPUS: 84857786388