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R-loops are cellular structures composed of an RNA/DNA hybrid, which is formed when the RNA hybridises to a complementary DNA strand and a displaced single-stranded DNA. R-loops have been detected in various organisms from bacteria to mammals and play crucial roles in regulating gene expression, DNA and histone modifications, immunoglobulin class switch recombination, DNA replication, and genome stability. Recent evidence suggests that R-loops are also involved in molecular mechanisms of neurological diseases and cancer. In addition, mutations in factors implicated in R-loop biology, such as RNase H and SETX (senataxin), lead to devastating human neurodegenerative disorders, highlighting the importance of correctly regulating the level of R-loops in human cells. In this review we summarise current advances in this field, with a particular focus on diseases associated with dysregulation of R-loop structures. We also discuss potential therapeutic approaches for such diseases and highlight future research directions.

Original publication

DOI

10.1371/journal.pgen.1004630

Type

Journal article

Journal

PLoS Genet

Publication Date

09/2014

Volume

10

Keywords

Animals, Base Pairing, DNA, Single-Stranded, Gene Expression Regulation, Genetic Association Studies, Genetic Predisposition to Disease, Genetic Therapy, Humans, Protein Binding, RNA