TARLOOP SIGNED
R-loops as a major modulator of transcription-associated recombination and chromatin dynamics
Total Cost €
0EC-Contrib. €
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Project "TARLOOP" data sheet
The following table provides information about the project.
| Coordinator |
UNIVERSIDAD DE SEVILLA
Organization address contact info |
| 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.
| # | ||||
|---|---|---|---|---|
| 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 |
|---|---|---|---|
| 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 GarcÃa-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, MarÃa GarcÃa-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 GarcÃa-Pichardo, Juan C. Cañas, MarÃa L. GarcÃa-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 GarcÃa-BenÃtez, 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, MarÃa L. GarcÃa-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 Salasâ€Armenteros, Carmen Pérezâ€Calero, Aleix Bayonaâ€Feliu, Emanuela Tumini, Rosa Luna, Andrés Aguilera Human THO–Sin3A interaction reveals new mechanisms to prevent Râ€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 GarcÃa-BenÃtez, 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 |
MarÃa GarcÃa-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 GarcÃa-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, MarÃa GarcÃa-Rubio, Gerhard Seisenbacher, Andrés Aguilera, Eulà lia 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 |
MarÃa D Cubiles, Sonia Barroso, MarÃa 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 MartÃn-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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