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Removal of nascent transcripts by TTF2 is required for efficient sister chromatid resolution in human cells
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During mitosis, chromosome assembly is accompanied by a global shutdown of transcriptional activity. However, the contribution of mitotic transcriptional silencing to mitotic fidelity and genome stability remains poorly understood. Here, we used depletion of the Transcription Termination Factor 2 (TTF2) – a key factor in mitotic transcriptional inactivation – to investigate the impact of pervasive transcription on mitotic fidelity. TTF2 depletion leads to the accumulation of elongating transcripts on mitotic chromatin and triggers a spectrum of mitotic defects, including abnormal chromosome alignment, delayed progression, and impaired chromosome compaction. Among these, defects in sister chromatid resolution are particularly prominent, with DNA bridges emerging as the major segregation error and resulting in increased micronuclei formation. We further show that these defects are linked to changes in chromatin organisation, including R-loops accumulation. Importantly, most anaphase defects are significantly suppressed when transcription is chemically inhibited, establishing a causal link between transcriptional engagement during mitosis and the observed mitotic defects. Our findings reveal how abnormal retention of transcriptional activity on mitotic chromatin disrupts multiple mitotic processes, with impaired sister chromatid resolution representing a key pathway linking transcriptional dysregulation to genome instability.
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Citação
Tovini, L., Milagre, I., Peneda, C., & Oliveira, R. A. (2026). Removal of nascent transcripts by TTF2 is required for efficient sister chromatid resolution in human cells. bioRxiv. https://doi.org/10.64898/2026.01.26.701825
Editora
bioRxiv