کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5533099 | 1550355 | 2017 | 13 صفحه PDF | دانلود رایگان |
- R-loop resolution defects are found to be associated with an increasing number of diseases.
- R-loop-dependent genomic instability appears to be a common denominator in many cancers and neurological disorders.
- R loops likely trigger chromatin state changes at certain disease-associated genes.
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.
Graphical Abstract114
Journal: Journal of Molecular Biology - Volume 429, Issue 21, 27 October 2017, Pages 3168-3180