dc.creator | Bayona Feliu, Aleix | es |
dc.creator | Herrera Moyano, Emilia | es |
dc.creator | Badra Fajardo, Nibal | es |
dc.creator | Galván Femenía, Iván | es |
dc.creator | Soler Oliva, María Eugenia | |
dc.creator | Aguilera López, Andrés | |
dc.date.accessioned | 2023-11-24T11:59:29Z | |
dc.date.available | 2023-11-24T11:59:29Z | |
dc.date.issued | 2023 | |
dc.identifier.citation | Bayona Feliu, A., Herrera Moyano, E., Badra Fajardo, N., Galván Femenía, I., Soler Oliva, M.E. y Aguilera López, A. (2023). The chromatin network helps prevent cancer-associated mutagenesis at transcription-replication conflicts. Nature Communications, 14 (1), 6890. https://doi.org/10.1038/s41467-023-42653-0. | |
dc.identifier.issn | 2041-1723 | es |
dc.identifier.uri | https://hdl.handle.net/11441/151567 | |
dc.description.abstract | Genome instability is a feature of cancer cells, transcription being an important
source of DNA damage. This is in large part associated with R-loops, which
hamper replication, especially at head-on transcription-replication conflicts
(TRCs). Here we show that TRCs trigger a DNA Damage Response (DDR)
involving the chromatin network to prevent genome instability. Depletion of
the key chromatin factors INO80, SMARCA5 and MTA2 results in TRCs, fork
stalling and R-loop-mediated DNA damage which mostly accumulates at S/G2,
while histone H3 Ser10 phosphorylation, a mark of chromatin compaction, is
enriched at TRCs. Strikingly, TRC regions show increased mutagenesis in
cancer cells with signatures of homologous recombination deficiency,
transcription-coupled nucleotide excision repair (TC-NER) and of the AID/
APOBEC cytidine deaminases, being predominant at head-on collisions. Thus,
our results support that the chromatin network prevents R-loops and TRCs
from genomic instability and mutagenic signatures frequently associated
with cancer. | es |
dc.description.sponsorship | MCIN/AEI/10.13039/501100011033 - I + D + i PID2019-104270GB-I00/BMC | es |
dc.description.sponsorship | Consejo Europeo de Investigación - ERC2014 AdG669898 TARLOOP | es |
dc.format | application/pdf | es |
dc.format.extent | 16 p. | es |
dc.language.iso | eng | es |
dc.publisher | Nature Research | es |
dc.relation.ispartof | Nature Communications, 14 (1), 6890. | |
dc.rights | Atribución 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.title | The chromatin network helps prevent cancer-associated mutagenesis at transcription-replication conflicts | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Genética | es |
dc.relation.projectID | PID2019-104270GB-I00/BMC | es |
dc.relation.projectID | ERC2014 AdG669898 TARLOOP | es |
dc.relation.publisherversion | https://doi.org/10.1038/s41467-023-42653-0 | es |
dc.identifier.doi | 10.1038/s41467-023-42653-0 | es |
dc.journaltitle | Nature Communications | es |
dc.publication.volumen | 14 | es |
dc.publication.issue | 1 | es |
dc.publication.initialPage | 6890 | es |
dc.contributor.funder | Ministerio de Ciencia e Innovación (MICIN). España | es |
dc.contributor.funder | Agencia Estatal de Investigación. España | es |
dc.contributor.funder | European Research Council (ERC) | es |