Miniatura

Fitxers

ZhangXW.pdf (1.6 MB)

Tipus de document

Article

Versió

Versió publicada

Data de publicació

2017-06-26

Llicència de publicació

cc by (c) Zhang et al., 2017
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/124353

Attenuation of RNA polymerase II pausing mitigates BRCA1-associated R-loop accumulation and tumorigenesis

Títol de la revista

Autors

Director/Tutor

ISSN de la revista

Títol del volum

Recurs relacionat

https://doi.org/10.1038/ncomms15908

Resum

Most BRCA1-associated breast tumours are basal-like yet originate from luminal progenitors. BRCA1 is best known for its functions in double-strand break repair and resolution of DNA replication stress. However, it is unclear whether loss of these ubiquitously important functions fully explains the cell lineage-specific tumorigenesis. In vitro studies implicate BRCA1 in elimination of R-loops, DNA-RNA hybrid structures involved in transcription and genetic instability. Here we show that R-loops accumulate preferentially in breast luminal epithelial cells, not in basal epithelial or stromal cells, of BRCA1 mutation carriers. Furthermore, R-loops are enriched at the 50 end of those genes with promoter-proximal RNA polymerase II (Pol II) pausing. Genetic ablation of Cobra1, which encodes a Pol II-pausing and BRCA1-binding protein, ameliorates R-loop accumulation and reduces tumorigenesis in Brca1-knockout mouse mammary epithelium. Our studies show that Pol II pausing is an important contributor to BRCA1-associated R-loop accumulation and breast cancer development.

Matèries

Càncer de mama

Matèries (anglès)

Breast cancer

Citació

Col·leccions

Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

ZHANG, Xiaowen, CHIANG, Huai-chin, WANG, Yao, ZHANG, Chi, SMITH, Sabrina, ZHAO, Xiayan, NAIR, Sreejith j., MICHALEK, Joel, JATOI, Ismail, LAUTNER, Meeghan, OLIVER, Boyce, WANG, Howard, PETIT, Anna, SOLER, María teresa, BRUNET, Joan, MATEO GONZÁLEZ, Francesca, PUJANA GENESTAR, M. ángel, POGGI, Elizabeth, CHALDEKAS, Krysta, ISAACS, Claudine, PESHKIN, Beth n., OCHOA, Oscar, CHEDIN, Frederic, THEOHARIS, Constantine, SUN, Lu-zhe, CURIEL, Tyler j., ELLEDGE, Richard, JIN, Victor x., HU, Yanfen, LI, Rong. Attenuation of RNA polymerase II pausing mitigates BRCA1-associated R-loop accumulation and tumorigenesis. _Nature Communications_. 2017. Vol. 8. [consulta: 23 de gener de 2026]. [Disponible a: https://hdl.handle.net/2445/124353]

Exportar metadades

JSON - METS

Compartir registre