Roles for Pbp1 and Caloric Restriction in Genome and Lifespan Maintenance via Suppression of RNA-DNA Hybrids

•Yeast ataxin-2 protein Pbp1 represses deleterious noncoding RNA-DNA hybrids•Deletion of G quadruplex DNA-stabilizing Stm1 abolishes RNA-DNA in pbp1Δ cells•Caloric restriction suppresses RNA-DNA in pbp1Δ cells via RNaseH and Pif1 helicase•RNA-DNA hybrid repression maintains replicative lifespan

SummaryIntergenic transcription within repetitive loci such as the ribosomal DNA (rDNA) repeats of yeast commonly triggers aberrant recombination. Major mechanisms suppressing aberrant rDNA recombination rely on chromatin silencing or RNAPII repression at intergenic spacers within the repeats. We find ancient processes operating at rDNA intergenic spacers and other loci to maintain genome stability via repression of RNA-DNA hybrids. The yeast Ataxin-2 protein Pbp1 binds noncoding RNA, suppresses RNA-DNA hybrids, and prevents aberrant rDNA recombination. Repression of RNA-DNA hybrids in Pbp1-deficient cells through RNaseH overexpression, deletion of the G4DNA-stabilizing Stm1, or caloric restriction operating via RNaseH/Pif1 restores rDNA stability. Pbp1 also limits hybrids at non-rDNA G4DNA loci including telomeres. Moreover, cells lacking Pbp1 have a short replicative lifespan that is extended upon hybrid suppression. Thus, we find roles for Pbp1 in genome maintenance and reveal that caloric restriction counteracts Pbp1 deficiencies by engaging RNaseH and Pif1.

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