E-viri
Recenzirano
Odprti dostop
-
Hatchi, Elodie; Skourti-Stathaki, Konstantina; Ventz, Steffen; Pinello, Luca; Yen, Angela; Kamieniarz-Gdula, Kinga; Dimitrov, Stoil; Pathania, Shailja; McKinney, Kristine M.; Eaton, Matthew L.; Kellis, Manolis; Hill, Sarah J.; Parmigiani, Giovanni; Proudfoot, Nicholas J.; Livingston, David M.
Molecular cell, 02/2015, Letnik: 57, Številka: 4Journal Article
The mechanisms contributing to transcription-associated genomic instability are both complex and incompletely understood. Although R-loops are normal transcriptional intermediates, they are also associated with genomic instability. Here, we show that BRCA1 is recruited to R-loops that form normally over a subset of transcription termination regions. There it mediates the recruitment of a specific, physiological binding partner, senataxin (SETX). Disruption of this complex led to R-loop-driven DNA damage at those loci as reflected by adjacent γ-H2AX accumulation and ssDNA breaks within the untranscribed strand of relevant R-loop structures. Genome-wide analysis revealed widespread BRCA1 binding enrichment at R-loop-rich termination regions (TRs) of actively transcribed genes. Strikingly, within some of these genes in BRCA1 null breast tumors, there are specific insertion/deletion mutations located close to R-loop-mediated BRCA1 binding sites within TRs. Thus, BRCA1/SETX complexes support a DNA repair mechanism that addresses R-loop-based DNA damage at transcriptional pause sites. Display omitted •Endogenous BRCA1 and senataxin (SETX) interact in a BRCA1-driven process•BRCA1/SETX complexes are recruited to R-loop-associated termination regions (TRs)•BRCA1/SETX complexes suppress transcriptional DNA damage arising at nearby R-loops•BRCA1 breast cancers reveal indel mutations near BRCA1 TR binding regions Transcriptional R-loops represent a potential threat to genome integrity. Hatchi et al. show that BRCA1, in partnership with SETX, is engaged in a DNA repair mechanism that deals with R-loop-associated genomic instability at transcriptional termination pause sites.
Avtor
![loading ... loading ...](themes/default/img/ajax-loading.gif)
Vnos na polico
Trajna povezava
- URL:
Faktor vpliva
Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Baze podatkov, v katerih je revija indeksirana
Ime baze podatkov | Področje | Leto |
---|
Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
---|
Vir: Osebne bibliografije
in: SICRIS
To gradivo vam je dostopno v celotnem besedilu. Če kljub temu želite naročiti gradivo, kliknite gumb Nadaljuj.