The G-rich Repeats in FMR1 and C9orf72 Loci Are Hotspots for Local Unpairing of DNA.

A new interesting article has been published in Genetics. 2018 Nov 5. pii: genetics.301672.2018. doi: 10.1534/genetics.118.301672. [Epub ahead of print] and titled:

The G-rich Repeats in FMR1 and C9orf72 Loci Are Hotspots for Local Unpairing of DNA.

Authors of this article are:

Abu Diab M, Mor-Shaked H, Cohen E, Cohen-Hadad Y, Ram O, Epsztejn-Litman S, Eiges R.

A summary of the article is shown below:

Pathological mutations involving noncoding microsatellite repeats are typically located near promoters in CpG islands and are coupled with extensive repeat instability when sufficiently long. What causes these regions to be prone to repeat instability is not fully understood. There is a general consensus that instability results from the induction of unusual structures in the DNA by the repeats as a consequence of mispairing between complementary strands. In addition, there is some evidence that repeat instability is mediated by RNA transcription through the formation of three-stranded nucleic structures composed of persistent DNA:RNA hybrids, concomitant with single strand DNA displacements (R-loops). Using human embryonic stem cells with wild type and repeat expanded alleles in the FMR1 (CGGs) and C9orf72 (GGGGCCs) genes, we show that these loci constitute preferential sites (hotspots) for DNA unpairing. When R-loops are formed, DNA unpairing is more extensive, and is coupled with the interruptions of double strand structures by the non-transcribing (G-rich) DNA strand. These interruptions are likely to reflect unusual structures in the DNA that drive repeat instability when the G-rich repeats considerably expand. Further, we demonstrate that when the CGGs in FMR1 are hypermethylated and transcriptionally inactive, local DNA unpairing is abolished. Our study thus takes one more step towards the identification of dynamic, unconventional DNA structures across the G-rich repeats at FMR1 and C9orf72 disease-associated loci.

Check out the article’s website on Pubmed for more information:

This article is a good source of information and a good way to become familiar with topics such as:

C9orf72;FMR1;R-loops;Unstable repeat expansions;single strand DNA displacements


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