Uracil overload triggers global genome instability and dUTPdysgenesis.

Uracil overload in Saccharomyces cerevisiae with attenuated DUT1 expression drives global genome instability, including aneuploidy and LOH, with dUTPdysgenesis causing G1-phase chromosomal shattering.

• Why it matters: Uracil accumulation threatens genomic integrity, but how uracil overload globally reshapes mutation, recombination, and chromosome changes—and how it can act across mating barriers—was unclear.
• What they did: The authors used DUT1-attenuated yeast strains to map point mutations, recombination, and aneuploidy, then tested UNG1 deletion and analyzed repair bottlenecks involving Ung1 and Apn1.
• The result: UNG1 deletion suppressed most induced mutations and LOH, while aneuploidy depended on intact genomic uracil; uracil lesions depleted Ung1/Apn1, shifting mutagenesis and recombination toward interstitial versus terminal LOH, and mating triggered dUTPdysgenesis.