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CODECHECK SIGNED

CRACKING THE CODE BEHIND MITOTIC FIDELITY: the roles of tubulin post-translational modifications and a chromosome separation checkpoint

Total Cost €

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EC-Contrib. €

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Partnership

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 CODECHECK project word cloud

Explore the words cloud of the CODECHECK project. It provides you a very rough idea of what is the project "CODECHECK" about.

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Project "CODECHECK" data sheet

The following table provides information about the project.

Coordinator
INSTITUTO DE BIOLOGIA MOLECULAR E CELULAR-IBMC 

Organization address
address: RUA ALFREDO ALLEN 208
city: PORTO
postcode: 4200 135
website: www.ibmc.up.pt

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Portugal [PT]
 Project website http://codecheck.i3s.up.pt
 Total cost 2˙323˙468 €
 EC max contribution 2˙323˙468 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-CoG
 Funding Scheme ERC-COG
 Starting year 2016
 Duration (year-month-day) from 2016-07-01   to  2021-06-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    INSTITUTO DE BIOLOGIA MOLECULAR E CELULAR-IBMC PT (PORTO) coordinator 2˙323˙468.00

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 Project objective

During the human lifetime 10000 trillion cell divisions take place to ensure tissue homeostasis and several vital functions in the organism. Mitosis is the process that ensures that dividing cells preserve the chromosome number of their progenitors, while deviation from this, a condition known as aneuploidy, represents the most common feature in human cancers. Here we will test two original concepts with strong implications for chromosome segregation fidelity. The first concept is based on the “tubulin code” hypothesis, which predicts that molecular motors “read” tubulin post-translational modifications on spindle microtubules. Our proof-of-concept experiments demonstrate that tubulin detyrosination works as a navigation system that guides chromosomes towards the cell equator. Thus, in addition to regulating the motors required for chromosome motion, the cell might regulate the tracks in which they move on. We will combine proteomic, super-resolution and live-cell microscopy, with in vitro reconstitutions, to perform a comprehensive survey of the tubulin code and the respective implications for motors involved in chromosome motion, mitotic spindle assembly and correction of kinetochore-microtubule attachments. The second concept is centered on the recently uncovered chromosome separation checkpoint mediated by a midzone-associated Aurora B gradient, which delays nuclear envelope reformation in response to incompletely separated chromosomes. We aim to identify Aurora B targets involved in the spatiotemporal regulation of the anaphase-telophase transition. We will establish powerful live-cell microscopy assays and a novel mammalian model system to dissect how this checkpoint allows the detection and correction of lagging/long chromosomes and DNA bridges that would otherwise contribute to genomic instability. Overall, this work will establish a paradigm shift in our understanding of how spatial information is conveyed to faithfully segregate chromosomes during mitosis.

 Publications

year authors and title journal last update
List of publications.
2019 Hugo Girão, Naoyuki Okada, Tony A. Rodrigues, Alexandra O. Silva, Ana C. Figueiredo, Zaira Garcia, Tatiana Moutinho-Santos, Ikuko Hayashi, Jorge E. Azevedo, Sandra Macedo-Ribeiro, Helder Maiato
CLASP2 binding to curved microtubule tips promotes flux and stabilizes kinetochore attachments
published pages: jcb.201905080, ISSN: 0021-9525, DOI: 10.1083/jcb.201905080
The Journal of Cell Biology 2020-04-08
2019 Olga Afonso, Colleen M Castellani, Liam P Cheeseman, Jorge G Ferreira, Bernardo Orr, Luisa T Ferreira, James J Chambers, Eurico Morais-de-Sá, Thomas J Maresca, Helder Maiato
Spatiotemporal control of mitotic exit during anaphase by an aurora B-Cdk1 crosstalk
published pages: , ISSN: 2050-084X, DOI: 10.7554/elife.47646
eLife 8 2020-04-08
2018 Danica Drpic, Ana C. Almeida, Paulo Aguiar, Fioranna Renda, Joana Damas, Harris A. Lewin, Denis M. Larkin, Alexey Khodjakov, Helder Maiato
Chromosome Segregation Is Biased by Kinetochore Size
published pages: , ISSN: 0960-9822, DOI: 10.1016/j.cub.2018.03.023
Current Biology 2020-04-08
2017 Helder Maiato, Ana Gomes, Filipe Sousa, Marin Barisic
Mechanisms of Chromosome Congression during Mitosis
published pages: 13, ISSN: 2079-7737, DOI: 10.3390/biology6010013
Biology 6/4 2020-04-08
2018 Swadhin Chandra Jana, Susana Mendonça, Pedro Machado, Sascha Werner, Jaqueline Rocha, António Pereira, Helder Maiato, Mónica Bettencourt-Dias
Differential regulation of transition zone and centriole proteins contributes to ciliary base diversity
published pages: 928-941, ISSN: 1465-7392, DOI: 10.1038/s41556-018-0132-1
Nature Cell Biology 20/8 2020-04-08
2019 Bernardo Orr, Helder Maiato
No chromosome left behind: The importance of metaphase alignment for mitotic fidelity
published pages: jcb.201902041, ISSN: 0021-9525, DOI: 10.1083/jcb.201902041
The Journal of Cell Biology 2020-04-08
2017 Ana C Figueiredo, Helder Maiato
Kinetochore regulation: Let there be light
published pages: 1058-1059, ISSN: 1552-4450, DOI: 10.1038/nchembio.2464
Nature Chemical Biology 13/10 2020-04-08
2019 António Pereira, Mafalda Sousa, Ana C. Almeida, Luísa T. Ferreira, Ana Rita Costa, Marco Novais-Cruz, Cristina Ferrás, Mónica Mendes Sousa, Paula Sampaio, Michael Belsley, Helder Maiato
Coherent-hybrid STED: high contrast sub-diffraction imaging using a bi-vortex depletion beam
published pages: 8092, ISSN: 1094-4087, DOI: 10.1364/oe.27.008092
Optics Express 27/6 2020-04-08
2017 Anna Akhmanova, Helder Maiato
Closing the tubulin detyrosination cycle
published pages: 1381-1382, ISSN: 0036-8075, DOI: 10.1126/science.aar3895
Science 358/6369 2020-04-08
2016 Kuan-Chung Su, Zachary Barry, Nina Schweizer, Helder Maiato, Mark Bathe, Iain McPherson Cheeseman
A Regulatory Switch Alters Chromosome Motions at the Metaphase-to-Anaphase Transition
published pages: 1728-1738, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2016.10.046
Cell Reports 17/7 2020-04-08
2018 Marco Novais-Cruz, Maria Alba Abad, Wilfred FJ van IJcken, Niels Galjart, A Arockia Jeyaprakash, Helder Maiato, Cristina Ferrás
Mitotic progression, arrest, exit or death relies on centromere structural integrity, rather than de novo transcription
published pages: , ISSN: 2050-084X, DOI: 10.7554/elife.36898
eLife 7 2020-04-08
2018 Ana C. Almeida, Helder Maiato
Chromokinesins
published pages: R1131-R1135, ISSN: 0960-9822, DOI: 10.1016/j.cub.2018.07.017
Current Biology 28/19 2020-04-08
2017 Helder Maiato, Cristina Ferrás
Actin divides to conquer
published pages: 756-757, ISSN: 0036-8075, DOI: 10.1126/science.aao2461
Science 357/6353 2020-04-08

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