Drugging the R-loop interactome: RNA-DNA hybrid binding proteins as targets for cancer therapy.
Cancer diagnostics and therapy
Chemotherapy
Clinical trial
Drug sensitivity
R-loop
RNA-DNA hybrid
Survival association
Journal
DNA repair
ISSN: 1568-7856
Titre abrégé: DNA Repair (Amst)
Pays: Netherlands
ID NLM: 101139138
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
02
03
2019
revised:
16
05
2019
accepted:
02
07
2019
pubmed:
14
7
2019
medline:
15
5
2020
entrez:
14
7
2019
Statut:
ppublish
Résumé
Unravelling the origin of genetic alterations from point mutations to chromosomal rearrangements was greatly enhanced by the discovery of RNA-DNA hybrids (R-loops) that behave as hotspots of genomic instability in a variety of organisms. Current models suggest that uncontrolled R-loops are a hazard to genome integrity, therefore, identifying proteins that are involved in recognising and signalling R-loop structures are of key importance. Herein we analysed key RNA-DNA hybrid binding proteins in humans taking advantage of large-scale gene expression, survival rate, and drug-sensitivity data from cancer genomics databases. We show that expression of RNA-DNA hybrid binding proteins in various cancer types is associated with survival and may have contrasting outcomes in responding to therapeutic treatments. Based on the revealed pharmacogenomic landscape of human RNA-DNA hybrid binding proteins, we propose that R-loops and R-loop binding proteins are potentially relevant new epigenetic markers and therapeutic targets in multiple cancers.
Identifiants
pubmed: 31300387
pii: S1568-7864(19)30069-2
doi: 10.1016/j.dnarep.2019.102642
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
DNA-Binding Proteins
0
RNA-Binding Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
102642Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.