Consequences of Impaired Mitotic Chromosome Silencing

Mitosis imposes a profound reorganisation of the genome, requiring the temporary silencing of transcriptional activity and its timely reactivation at mitotic exit. Although this balance is thought to be critical, the mechanisms and consequences of impaired mitotic silencing remain poorly defined. Here, we explore the impact of persistent transcription during mitosis and its influence on subsequent transcriptional reactivation. We show that when chromosomes fail to maintain transcriptional silence, nascent transcripts accumulate on mitotic chromatin, leading to defects in chromosome alignment, compaction, and sister chromatid resolution. These errors compromise mitotic fidelity, increasing segregation defects and genome instability. We further show that mitotic exit is perturbed by the premature reactivation of rRNA synthesis, which drives early nucleolar assembly. Together, our findings highlight the importance of robust transcriptional silencing during mitosis, not only for accurate chromosome segregation, but also for ensuring the orderly reactivation of transcriptional programs at mitotic exit.