Transcription termination safeguards quiescent chromatin for faithful cell-cycle re-entry.

While this G₀ state is universally associated with a compact chromatin organization, the active safeguards that preserve this structural template—and their necessity for future division competence and fidelity—remain unknown.

Here we show, using fission yeast as a model, that chromatin structural maintenance in quiescence requires the enforcement of transcription termination by the conserved factor Ppn1PNUTS/Ref2. We identify a minimal disordered region in Ppn1 that resolves a physical conflict in the quiescent genome by preventing the transcriptional “eviction” of cohesin. Loss of this safeguard drives a progressive structural erosion that deregulates cyclin dependent kinase (CDK) dynamics and causes lethal aneuploidy upon cell-cycle re-entry.