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R-loops at telomeres
Introduction
When the RNA polymerase traverses DNA during transcription it creates
torsion and compacts the DNA ahead (positive supercoiling) while relaxing the
DNA behind it (negative supercoiling). The topology is controlled by specific
topoisomerases. If the topology maintanence is disturbed, negative
supercoiling-induced relaxed DNA can basepair with the nascent RNA forming
RNA-DNA hybrid or R-loops. Any step that is involved in keeping the nascent
RNA from base pairing with DNA is important to prevent R-loops. R loops
formation can impair DNA replication and cause genomic stability (for a
review, see [80]).
Figure 7: A: During transcription by RNA Pol II, the local negative supercoiling
behind transcription bubble might facilitate transient ssDNA formation (represented by
stars). B: Defective mechanisms in controlling transcription bubble movement, ssDNA
formation or mRNA particle complex might lead to hybridization of RNA with the
template DNA forming a transient R-loop which if left unrepaired might cause genomic
instability (Source: [81])
Cells have RNAse enzymes, which cleave the RNA strand of the RNA–DNA
hybrids. In humans, mutations in genes encoding the subunits of the RNase H2
complex cause Aicardi-Goutières Syndrome, a congenital immune-mediated
neurodevelopmental disorder, and is generally fatal within the first few years
[82]. In yeast, RNH201 encodes the catalytic subunit of RNase H2p. RNases H
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