R-loops & regulatory changes in aging fission yeast drive non-random genome rearrangements

DNA breaks followed by chromosomal rearrangements that join non-neighbouring DNA sequences may critically affect gene function, evolution, and ageing. Such chromosomal rearrangements are difficult to spot in sequence data even if they are widespread, because they are individually rare and reflect diverse events. The Bähler lab reports sensitive analyses of DNA sequences and identifies prevalent rearrangements that specifically accumulate during ageing in yeast cells. These rearrangements feature short repeated DNA sequences near the breaks, preferentially occur in certain locations of the chromosomes (e.g., near their ends), and can link sequences originating from different chromosomes. They show results indicating that DNA-RNA interactions, triggered by the ageing-associated suppression of an RNA-binding protein, can cause the non-random patterns of some chromosomal rearrangements. These analyses suggest that similar patterns of chromosomal rearrangements accumulate in brain cells in older humans, raising the possibility that such DNA changes occurring in ageing cells are conserved from yeast to human.

https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1009784