Epigenetic repression suppresses genomic instability


Susan Gasser and her group at the FMI have found the pathway through which eukaryotic organisms protect their genomes from rearrangements and deletions that arise from repetitive DNA. Human genomes, like those of simple animals like worms, are filled with repeat sequences, many being remnants of viral infections of the distant past. This repetitive DNA is usually kept silent. The transcription of these repeats into RNA was shown by the Gasser laboratory to generate toxic hybrids between RNA and DNA. These aberrant "R-loops" can lead to deletions and insertions, endangering the integrity of the genome. Keeping them silent is the task of a universally conserved epigenetic modification on histone H3: the methylation of lysine 9. While this modification also silences genes during development, is was shown to be dispensable for tissue differentiation in C. elegans; instead it serves to protect the genome from repeat-driven mutation.

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