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Centromere Stability SIGNED

Mechanisms that maintain centromere DNA repeats stability in human cells.

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 Centromere Stability project word cloud

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

chromosomal    centromere    2017    division    dynamics    repetitive    chromatids    sister    subsequent    cancer    disease    cells    driving    connect    fellowship    qfish    separating    fragility    human    prevent    damage    assays    fluorescence    physiology    independent    age    defects    senescence    unveil    molecular    cas    compromised    aging    proteins    qrt    inducible    constitutive    play    giunta    aberrant    instability    replication    lines    mechanisms    pcr    undergoing    ideated    centromeres    fish    size    hybridization    aneuploidy    technique    editing    foundation    genome    arrays    crispr    spindle    funabiki    chromosomes    cell    barriers    aid    cen    stable    2018    rearrangements    circumvent    impeding    incomplete    chromosome    shortening    ccan    orientation    annotation    examine    mitosis    maintenance    framework    degron    network    sites    maintained    sequence    ploidy    poorly    array    dysfunction    situ    imaging    stability    innovative    cytogenetic    dna    throughput    primary    proliferation    validated    altogether    auxin    revealed    preventing    conceptual    lay    relies    cenp    cancers    co    variety    data   

Project "Centromere Stability" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITA DEGLI STUDI DI ROMA LA SAPIENZA 

Organization address
address: Piazzale Aldo Moro 5
city: ROMA
postcode: 185
website: www.uniroma1.it

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 Italy [IT]
 Total cost 183˙473 €
 EC max contribution 183˙473 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2018
 Funding Scheme MSCA-IF-EF-RI
 Starting year 2020
 Duration (year-month-day) from 2020-09-01   to  2022-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITA DEGLI STUDI DI ROMA LA SAPIENZA IT (ROMA) coordinator 183˙473.00

Map

 Project objective

Cell division relies on centromeres, which connect chromosomes to the spindle for separating sister chromatids in mitosis. Human centromeres are composed of large arrays of repetitive DNA, which are often sites of aberrant rearrangements in cancer. While centromere defects can cause chromosomal instability, the molecular mechanisms that maintain their repetitive DNA stable are poorly understood. During the fellowship, I aim to investigate how human centromere stability is maintained and the consequences of centromere dysfunction in driving cancer and aging. To circumvent impeding technical barriers due to incomplete centromere sequence annotation, I have ideated the use of Chromosome Orientation Fluorescence In Situ Hybridization at human centromeres (Cen-CO-FISH; Giunta, 2018). Using this innovative technique, I revealed that CENP-A and CCAN (constitutive centromere-associated network) proteins prevent centromere instability, and this functionality is compromised in cancer cell lines and in primary cells undergoing senescence (Giunta & Funabiki, 2017); my data show that CENP-A may play a new role during centromere replication, preventing DNA damage, repeats shortening, and subsequent aneuploidy. I will use the Auxin-Inducible Degron (AID) system and CRISPR-Cas genome editing with high-throughput imaging of Cen-CO-FISH to identify the human centromere maintenance network and investigate the mechanisms of repeats stability. I will also examine the consequences of centromeres dysfunction, including changes in the size of the array, cell ploidy and proliferation dynamics, using a variety of validated and novel methods, including Cen-qRT-PCR, qFISH and cytogenetic assays. Altogether, the proposed research will unveil a novel conceptual framework to explain the fragility of repetitive centromere DNA and its consequences on cell physiology and disease. This work will lay the foundation for my future independent research on centromere instability in age-associated cancers.

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The information about "CENTROMERE STABILITY" are provided by the European Opendata Portal: CORDIS opendata.

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