R Loops and Links to Human Disease.
Aberrant R-loop structures are increasingly being realized as an important contributor to human disease. R loops, which are mainly co-transcriptional, abundant RNA/DNA hybrids, form naturally and can indeed be beneficial for transcription regulation at certain loci. However, their unwanted persistence elsewhere or in particular situations can lead to DNA double-strand breaks, chromosome rearrangements, and hypermutation, which are all sources of genomic instability. Mutations in genes involved in R-loop resolution or mutations leading to R-loop formation at specific genes affect the normal physiology of the cell. We discuss here the examples of diseases for which a link with R loops has been described, as well as how disease-causing mutations might participate in the development and/or progression of diseases that include repeat-associated conditions, other neurological disorders, and cancers.
Department of Biological Sciences, Columbia University, New York, NY 10027, USA. Electronic address: pr2232@columbia.edu.
Patricia
P
Richard
Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
James L
JL
Manley
D004261:DNA Replication; D004194:Disease / Q000235:genetics*; D005786:Gene Expression Regulation; D042822:Genomic Instability; D006801:Humans; D009690:Nucleic Acid Conformation; D014158:Transcription, Genetic
R loops; chromatin reorganization; genomic instability; human diseases; transcription