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TARLOOP SIGNED

R-loops as a major modulator of transcription-associated recombination and chromatin dynamics

Total Cost €

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EC-Contrib. €

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Partnership

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 TARLOOP project word cloud

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

lines    prone    recombination    suggest    mechanisms    single    mrnp    impairment    biogenesis    rna    export    indicate    hybrid    conserved    resolution    tumorigenesis    decipher    cis    organism    cells    sequences    functional    plan    collisions    trans    understand    actively    works    double    formed    loop    intermediates    removal    suppressor    determinant    responsible    association    residues    tar    histone    biomedicine    cell    caenorhabditis    stranded    causes    observation    question    dna    accumulation    biology    linked    brca2    bacteria    structure    cerevisiae    instability    natural    human    mutation    probably    break    replication    fork    loops    cancer    dynamics    mediated    strand    understanding    tumor    model    transcription    genetic    proteins    elegans    mechanism    displaced    gene    prevention    chromatin    molecular    relevance    diseases    induce    source    genome    functions    genes    multidisciplinary    modulate    validated    acting    saccharomyces   

Project "TARLOOP" data sheet

The following table provides information about the project.

Coordinator
UNIVERSIDAD DE SEVILLA 

Organization address
address: CALLE S. FERNANDO 4
city: SEVILLA
postcode: 41004
website: www.us.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.cabimer.es/web3/en/research-groups/genome-instability-cancer/
 Total cost 2˙312˙500 €
 EC max contribution 2˙312˙500 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-ADG
 Funding Scheme ERC-ADG
 Starting year 2015
 Duration (year-month-day) from 2015-12-01   to  2021-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSIDAD DE SEVILLA ES (SEVILLA) coordinator 2˙312˙500.00

Map

 Project objective

Understanding the causes of genome instability, a condition linked to cancer and cancer-prone genetic diseases, is a major question in Molecular Biology and Biomedicine. Probably the most important natural cause of genome instability is transcription, which is known to induce both mutation and recombination from bacteria to human cells. Different studies suggest that transcription-associated recombination (TAR) is in large part due to collisions between transcription and replication, but increasing evidence indicate that R-loops, formed by a DNA-RNA hybrid and a displaced single-stranded DNA, may be a major determinant of genome instability. This is of particular relevance, provided our recent observation that tumor suppressor BRCA2 gene is involved in R-loop prevention/resolution and that, therefore, R-loops may represent a major potential source of tumorigenesis. The goal of this project is to understand the mechanisms of R-loop dynamics by identifying the functions and elements acting in cis and trans, that is, the DNA sequences and genes controlling R-loop formation and removal. The project will be based on a multidisciplinary approach using Saccharomyces cerevisiae and human cell lines. We plan: a) to identify the proteins and mechanism that actively works in the formation and prevention of intermediates responsible for R-loop-mediated TAR; b) to define the histone residues linked to R-loop formation and its role in chromatin dynamics, and c) to establish how the different trans and cis elements control genome-wide R-loop–mediated genome instability whether or not in association with replication fork impairment, double-strand break accumulation, chromatin structure and mRNP biogenesis and export. The functional relevance of selected conserved genes will be validated in Caenorhabditis elegans as a model organism. The long-term objective of the proposal is to decipher the mechanisms by which R-loops modulate chromatin dynamics and genome instability.

 Publications

year authors and title journal last update
List of publications.
2019 Pedro Ortega, Belén Gómez-González, Andrés Aguilera
Rpd3L and Hda1 histone deacetylases facilitate repair of broken forks by promoting sister chromatid cohesion
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-019-13210-5
Nature Communications 10/1 2020-02-13
2019 Irene Salas-Armenteros, Sonia I. Barroso, Ana G. Rondón, Mónica Pérez, Eloisa Andújar, Rosa Luna, Andrés Aguilera
Depletion of the MFAP1/SPP381 Splicing Factor Causes R-Loop-Independent Genome Instability
published pages: 1551-1563.e7, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2019.07.010
Cell Reports 28/6 2020-02-13
2019 Tatiana García-Muse, Andrés Aguilera
R Loops: From Physiological to Pathological Roles
published pages: 604-618, ISSN: 0092-8674, DOI: 10.1016/j.cell.2019.08.055
Cell 179/3 2020-02-13
2019 Diana Zatreanu, Zhong Han, Richard Mitter, Emanuela Tumini, Hannah Williams, Lea Gregersen, A. Barbara Dirac-Svejstrup, Stefania Roma, Aengus Stewart, Andres Aguilera, Jesper Q. Svejstrup
Elongation Factor TFIIS Prevents Transcription Stress and R-Loop Accumulation to Maintain Genome Stability
published pages: 57-69.e9, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2019.07.037
Molecular Cell 76/1 2020-02-13
2017 Sandra Muñoz-Galván, María García-Rubio, Pedro Ortega, Jose F. Ruiz, Sonia Jimeno, Benjamin Pardo, Belén Gómez-González, Andrés Aguilera
A new role for Rrm3 in repair of replication-born DNA breakage by sister chromatid recombination
published pages: e1006781, ISSN: 1553-7390, DOI: 10.1371/journal.pgen.1006781
PLOS Genetics 13/5 2019-10-01
2017 Desiré García-Pichardo, Juan C. Cañas, María L. García-Rubio, Belén Gómez-González, Ana G. Rondón, Andrés Aguilera
Histone Mutants Separate R Loop Formation from Genome Instability Induction
published pages: 597-609.e5, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2017.05.014
Molecular Cell 66/5 2019-10-01
2016 Emanuela Tumini, Sonia Barroso, Carmen Pérez -Calero, Andrés Aguilera
Roles of human POLD1 and POLD3 in genome stability
published pages: , ISSN: 2045-2322, DOI: 10.1038/srep38873
Scientific Reports 6/1 2019-10-01
2017 Francisco García-Benítez, Hélène Gaillard, Andrés Aguilera
Physical proximity of chromatin to nuclear pores prevents harmful R loop accumulation contributing to maintain genome stability
published pages: 10942-10947, ISSN: 0027-8424, DOI: 10.1073/pnas.1707845114
Proceedings of the National Academy of Sciences 114/41 2019-10-01
2016 Advaitha Madireddy, Settapong T. Kosiyatrakul, Rebecca A. Boisvert, Emilia Herrera-Moyano, María L. García-Rubio, Jeannine Gerhardt, Elizabeth A. Vuono, Nichole Owen, Zi Yan, Susan Olson, Andrés Aguilera, Niall G. Howlett, Carl L. Schildkraut
FANCD2 Facilitates Replication through Common Fragile Sites
published pages: 388-404, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2016.09.017
Molecular Cell 64/2 2019-10-01
2017 Belén Gómez-González, Andrés Aguilera
The need to regulate replication fork speed
published pages: 722-723, ISSN: 0036-8075, DOI: 10.1126/science.aaq0678
Science 358/6364 2019-10-01
2017 Irene Salas‐Armenteros, Carmen Pérez‐Calero, Aleix Bayona‐Feliu, Emanuela Tumini, Rosa Luna, Andrés Aguilera
Human THO–Sin3A interaction reveals new mechanisms to prevent R‐loops that cause genome instability
published pages: 3532-3547, ISSN: 0261-4189, DOI: 10.15252/embj.201797208
The EMBO Journal 36/23 2019-10-01
2017 Hélène Gaillard, Francisco García-Benítez, Andrés Aguilera
Gene gating at nuclear pores prevents the formation of R loops
published pages: e1405140, ISSN: 2372-3556, DOI: 10.1080/23723556.2017.1405140
Molecular & Cellular Oncology 5/1 2019-10-01
2018 María García-Rubio, Paula Aguilera, Juan Lafuente-Barquero, José F. Ruiz, Marie-Noelle Simon, Vincent Geli, Ana G. Rondón, Andrés Aguilera
Yra1-bound RNA–DNA hybrids cause orientation-independent transcription–replication collisions and telomere instability
published pages: 965-977, ISSN: 0890-9369, DOI: 10.1101/gad.311274.117
Genes & Development 32/13-14 2019-10-01
2016 Hélène Gaillard, Andrés Aguilera
Transcription as a Threat to Genome Integrity
published pages: 291-317, ISSN: 0066-4154, DOI: 10.1146/annurev-biochem-060815-014908
Annual Review of Biochemistry 85/1 2019-10-01
2017 Juan Lafuente-Barquero, Sarah Luke-Glaser, Marco Graf, Sonia Silva, Belén Gómez-González, Arianna Lockhart, Michael Lisby, Andrés Aguilera, Brian Luke
The Smc5/6 complex regulates the yeast Mph1 helicase at RNA-DNA hybrid-mediated DNA damage
published pages: e1007136, ISSN: 1553-7404, DOI: 10.1371/journal.pgen.1007136
PLOS Genetics 13/12 2019-10-01
2016 Tatiana García-Muse, Andrés Aguilera
Transcription–replication conflicts: how they occur and how they are resolved
published pages: 553-563, ISSN: 1471-0072, DOI: 10.1038/nrm.2016.88
Nature Reviews Molecular Cell Biology 17/9 2019-10-01
2018 Alba Duch, Berta Canal, Sonia I. Barroso, María García-Rubio, Gerhard Seisenbacher, Andrés Aguilera, Eulàlia de Nadal, Francesc Posas
Multiple signaling kinases target Mrc1 to prevent genomic instability triggered by transcription-replication conflicts
published pages: 379, ISSN: 2041-1723, DOI: 10.1038/s41467-017-02756-x
Nature Communications 9/1 2019-10-01
2017 Andrés Aguilera, Belén Gómez-González
DNA–RNA hybrids: the risks of DNA breakage during transcription
published pages: 439-443, ISSN: 1545-9993, DOI: 10.1038/nsmb.3395
Nature Structural & Molecular Biology 24/5 2019-10-01
2018 María D Cubiles, Sonia Barroso, María I Vaquero-Sedas, Alicia Enguix, Andrés Aguilera, Miguel A Vega-Palas
Epigenetic features of human telomeres
published pages: 2347-2355, ISSN: 0305-1048, DOI: 10.1093/nar/gky006
Nucleic Acids Research 46/5 2019-10-01
2017 Vaibhav Bhatia, Emilia Herrera-Moyano, Andres Aguilera, Belen Gomez-Gonzalez
The Role of Replication-Associated Repair Factors on R-Loops
published pages: 171, ISSN: 2073-4425, DOI: 10.3390/genes8070171
Genes 8/7 2019-10-01
2019 Tatiana Garcia-Muse, U. Galindo-Diaz, M. Garcia-Rubio, J.S. Martin, J. Polanowska, N. O’Reilly, A. Aguilera, Simon J. Boulton
A Meiotic Checkpoint Alters Repair Partner Bias to Permit Inter-sister Repair of Persistent DSBs
published pages: 775-787.e5, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2018.12.074
Cell Reports 26/3 2019-10-01
2019 Hélène Gaillard, José M Santos-Pereira, Andrés Aguilera
The Nup84 complex coordinates the DNA damage response to warrant genome integrity
published pages: 4054-4067, ISSN: 0305-1048, DOI: 10.1093/nar/gkz066
Nucleic Acids Research 47/8 2019-10-01
2019 Emanuela Tumini, Emilia Herrera-Moyano, Marta San Martín-Alonso, Sonia Barroso, Carlos M. Galmarini, Andrés Aguilera
The Antitumor Drugs Trabectedin and Lurbinectedin Induce Transcription-Dependent Replication Stress and Genome Instability
published pages: 773-782, ISSN: 1541-7786, DOI: 10.1158/1541-7786.mcr-18-0575
Molecular Cancer Research 17/3 2019-10-01
2018 Sonia Silva, Lola P. Camino, Andrés Aguilera
Human mitochondrial degradosome prevents harmful mitochondrial R loops and mitochondrial genome instability
published pages: 11024-11029, ISSN: 0027-8424, DOI: 10.1073/pnas.1807258115
Proceedings of the National Academy of Sciences 115/43 2019-10-01

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