Chromosome Instability & Dynamics
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.
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).
Inducible fluorescent speckle microscopy. Journal of Cell Biology212(2):245-255, 2016. [Journal: Article] [CI: 2] [IF: 8]
DOI: 10.1083/jcb.201506128 SCOPUS: 84959490543. .
Schweizer N., Pawar N., Weiss M., Maiato H.,
An organelle-exclusion envelope assists mitosis and underlies distinct molecular crowding in the spindle region. Journal of Cell Biology210(5):695-704, 2015. [Journal: Article] [CI: 33] [IF: 8,7]
DOI: 10.1083/jcb.201506107 SCOPUS: 84958572571. .
Drpic D., Pereira A.J., Barisic M., Maresca T.J., Maiato H.,
Polar Ejection Forces Promote the Conversion from Lateral to End-on Kinetochore-Microtubule Attachments on Mono-oriented Chromosomes. Cell Reports13(3):460-468, 2015. [Journal: Article] [CI: 16] [IF: 7,9]
DOI: 10.1016/j.celrep.2015.08.008 SCOPUS: 84944683483. .
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: 115] [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: 72] [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: 57] [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: 81] [IF: 19,7]
DOI: 10.1038/ncb2958 SCOPUS: 84899790283. .
Schweizer N., Ferrás C., Kern D.M., Logarinho E., Cheeseman I.M., Maiato H.,
Spindle assembly checkpoint robustness requires Tpr-mediated regulation of Mad1/Mad2 proteostasis. Journal of Cell Biology203(6):883-893, 2013. [Journal: Article] [CI: 39] [IF: 9,7]
DOI: 10.1083/jcb.201309076 SCOPUS: 84893406409. .
Moutinho-Pereira S., Stuurman N., Afonso O., Hornsveld M., Aguiar P., Goshima G., Vale R.D., Maiato H.,
Genes involved in centrosome-independent mitotic spindle assembly in Drosophila S2 cells. Proceedings of the National Academy of Sciences of the United States of America110(49):19808-19813, 2013. [Journal: Article] [CI: 31] [IF: 9,8]
DOI: 10.1073/pnas.1320013110 SCOPUS: 84889661951. .
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: 58] [IF: 20,8]
DOI: 10.1038/ncb2423 SCOPUS: 84857786388. .