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Mechan-of-Chromo SIGNED

Unfolding the Mechanism of Chromosome Cohesion and Condensation using Single-Molecule Biophysical Approaches

Total Cost €

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EC-Contrib. €

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Partnership

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 Mechan-of-Chromo project word cloud

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

unknown    proteins    regulated    protein    cohesion    global    optical    condensing    video    act    accessory    assays    experiments    spo0j    mt    architecture    revealed    forces    interrogate    molecule    models    decade    functions    function    discoveries    breakthroughs    despite    possibilities    devised    action    interactions    hypothetical    loaders    condensation    biological    fluorescence    combined    sites    structural    loaded    independent    physiological    subunits    poorly    monitoring    single    vivo    biochemical    hydrolysis    inspired    mechanical    stabilize    binding    maintenance    fundamentally    buffer    nature    vitro    magnetic    variant    manipulation    biophysical    opened    trapping    complexes    tweezers    smc    throughput    series    suited    chromatin    distant    capitulating    largely    individual    sequences    fast    discovery    pars    solutions    imaging    chromosome    applicable    repair    molecules    centres    folding    mechanism    atp    sm    difficulty    carefully    mediated    re    specialized    rationale    dna    organisation   

Project "Mechan-of-Chromo" data sheet

The following table provides information about the project.

Coordinator
AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS 

Organization address
address: CALLE SERRANO 117
city: MADRID
postcode: 28006
website: http://www.csic.es

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 Spain [ES]
 Project website http://www.fernandomorenoherrero.com
 Total cost 1˙894˙999 €
 EC max contribution 1˙894˙999 € (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 2016-06-01   to  2021-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS ES (MADRID) coordinator 1˙894˙999.00

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 Project objective

The global folding of the chromosome is mediated by Structural Maintenance of Chromosome (SMC) proteins, which stabilize the higher-order chromatin architecture by bringing distant DNA sequences together. Despite over a decade of work on these systems, their mechanism remains unknown, largely because of difficulty in re-capitulating physiological DNA binding and condensation in vitro. Moreover, traditional biochemical approaches are poorly suited for the study of processes that are fundamentally mechanical in nature. However, key breakthroughs, including the discovery that SMC is loaded by Spo0J protein at parS sites in vivo, and that parS sites act as global condensation centres for the chromosome have opened new possibilities to study chromosome organisation using single-molecule (SM) approaches. Importantly, our recent experiments with Magnetic Tweezers (MT) have already revealed a novel function of Spo0J in condensing DNA via a parS-independent binding mechanism.

Inspired by these recent discoveries, I have devised a series of novel SM biophysical approaches with the ambitious goal of determining the mechanism of action of SMC complexes, including understanding the role of SMC loaders and SMC accessory subunits, and how these proteins are regulated by ATP binding and hydrolysis for chromosome organisation. The rationale behind this approach is that SM methods are particularly well-suited for monitoring DNA cohesion and condensation where manipulation of individual DNA molecules, measurement of forces, and addition of proteins and buffer solutions can be carefully controlled. High throughput MT will be combined with fast video imaging, optical trapping, and fluorescence; and will be used to interrogate hypothetical models for SMC-DNA interactions. Finally, the novel assays developed here may be applicable to other protein-DNA interactions including variant SMC-like proteins specialized for other biological functions such as DNA repair.

 Publications

year authors and title journal last update
List of publications.
2019 Alberto Marin-Gonzalez, J. G. Vilhena, Fernando Moreno-Herrero, Ruben Perez
DNA Crookedness Regulates DNA Mechanical Properties at Short Length Scales
published pages: , ISSN: 0031-9007, DOI: 10.1103/physrevlett.122.048102
Physical Review Letters 122/4 2019-09-04
2019 Julene Madariaga-Marcos, Cesar L Pastrana, Gemma LM Fisher, Mark Simon Dillingham, Fernando Moreno-Herrero
ParB dynamics and the critical role of the CTD in DNA condensation unveiled by combined force-fluorescence measurements
published pages: , ISSN: 2050-084X, DOI: 10.7554/elife.43812
eLife 8 2019-09-04
2018 R. Arroyo, A. Martín-González, M. Echaide, A. Jain, W.H. Brondyk, J. Rosenbaum, F. Moreno-Herrero, J. Pérez-Gil
Supramolecular Assembly of Human Pulmonary Surfactant Protein SP-D
published pages: 1495-1509, ISSN: 0022-2836, DOI: 10.1016/j.jmb.2018.03.027
Journal of Molecular Biology 430/10 2019-05-09
2018 Bárbara Martín-García, Alejandro Martín-González, Carolina Carrasco, Ana M Hernández-Arriaga, Rubén Ruíz-Quero, Ramón Díaz-Orejas, Clara Aicart-Ramos, Fernando Moreno-Herrero, María A Oliva
The TubR–centromere complex adopts a double-ring segrosome structure in Type III partition systems
published pages: 5704-5716, ISSN: 0305-1048, DOI: 10.1093/nar/gky370
Nucleic Acids Research 46/11 2019-05-09
2019 Oliver J Wilkinson, Alejandro Martín-González, Haejoo Kang, Sarah J Northall, Dale B Wigley, Fernando Moreno-Herrero, Mark Simon Dillingham
CtIP forms a tetrameric dumbbell-shaped particle which bridges complex DNA end structures for double-strand break repair
published pages: , ISSN: 2050-084X, DOI: 10.7554/elife.42129
eLife 8 2019-05-09
2017 Alberto Marin-Gonzalez, J. G. Vilhena, Ruben Perez, Fernando Moreno-Herrero
Understanding the mechanical response of double-stranded DNA and RNA under constant stretching forces using all-atom molecular dynamics
published pages: 7049-7054, ISSN: 0027-8424, DOI: 10.1073/pnas.1705642114
Proceedings of the National Academy of Sciences 114/27 2019-06-18
2017 Gemma LM Fisher, César L Pastrana, Victoria A Higman, Alan Koh, James A Taylor, Annika Butterer, Timothy Craggs, Frank Sobott, Heath Murray, Matthew P Crump, Fernando Moreno-Herrero, Mark S Dillingham
The structural basis for dynamic DNA binding and bridging interactions which condense the bacterial centromere
published pages: , ISSN: 2050-084X, DOI: 10.7554/eLife.28086
eLife 6 2019-06-18
2018 J. Madariaga-Marcos, S. Hormeño, C. L. Pastrana, G. L. M. Fisher, M. S. Dillingham, F. Moreno-Herrero
Force determination in lateral magnetic tweezers combined with TIRF microscopy
published pages: 4579-4590, ISSN: 2040-3364, DOI: 10.1039/c7nr07344e
Nanoscale 10/9 2019-06-18

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