Referencia

Mol Cell. 2013. Nov 21;52(4):583-90.

Autores

Maikel Castellano-Pozo, José María Santos-Pereira, Ana García-Rondón, Sonia Barroso, Eloísa Andújar, Mónica Pérez-Alegre, Tatiana García-Muse y Andrés Aguilera.

Resumen

R loops are transcription byproducts that constitute a threat to genome integrity. Here we show that R loops are tightly linked to histone H3 S10 phosphorylation (H3S10P), a mark of chromatin condensation. Chromatin immunoprecipitation (ChIP)-on-chip (ChIP-chip) analyses reveal H3S10P accumulation at centromeres, pericentromeric chromatin, and a large number of active open reading frames (ORFs) in R-loop-accumulating yeast cells, better observed in G1. Histone H3S10 plays a key role in maintaining genome stability, as scored by ectopic recombination and plasmid loss, Rad52 foci, and Rad53 checkpoint activation. H3S10P coincides with the presence of DNA-RNA hybrids, is suppressed by ribonuclease H overexpression, and causes reduced accessibility of restriction endonucleases, implying a tight connection between R loops, H3S10P, and chromatin compaction. Such histone modifications were also observed in R-loop-accumulating Caenorhabditis elegans and HeLa cells. We therefore provide a role of RNA in chromatin structure essential to understand how R loops modulate genome dynamics.

Descripción

El artículo muestra que la acumulación de híbridos de RNA-DNA promueve la fosforilación de la serina 10 de la histona H3 (H3S10P) y la condensación de la cromatina en Saccharomyces, Caenorhabditis y células humanas. Igualmente dichos híbridos promueven la dimetilación de la lisina 9 de dicha histona. El trabajo no solo implica por primera vez un papel activo de los híbridos RNA-DNA en la estructura de la cromatina sino que sugiere que la fragilidad cromosómica ligada a híbridos RNA-DNA en eucariotas es debida en parte a la incapacidad de replicar correctamente regiones condensadas de cromatina.

grupo

REFERENCIA DEL GRUPO INVESTIGADOR

El grupo de “Inestabilidad Genómica” dirigido por Andrés Aguilera en CABIMER investiga las causas y consecuencias de la inestabilidad genética y su relación con otros procesos biológicos en S. Cerevisiae, C. elegans y en células humanas. Trata de identificar los factores y mecanismos que desencadenan estrés replicativo y fallos en la reparación, poniendo énfasis en aquellos asociados a la transcripción y metabolismo del ARN, incluida la formación de híbridos RNA-DNA que amenazan la integridad de los genomas y dan lugar a procesos cancerígenos.

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