Chromosome Dynamics Lab @ Católica Biomedical Research. Aiming to understand how mitotic chromosomes are assembled and influence mitotic fidelity

Joined October 2015
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🧵1/ Excited to share our new preprint! We uncover a new layer of control in how cells restart transcription after mitosis. 👉 TTF2 prevents premature rRNA transcription during mitotic exit (biorxiv.org/content/10.64898…)
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🧵1/ Excited to share our new preprint! We uncover a new layer of control in how cells restart transcription after mitosis. 👉 TTF2 prevents premature rRNA transcription during mitotic exit (biorxiv.org/content/10.64898…)
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12/ Huge congratulations to the great team: @catarinaapedro @MicrodotLaura @peneda_catarina and Mia.
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12/ Preprint here 👇 (biorxiv.org/content/10.64898…) Would love feedback!

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10/ Our work links two fields that often don’t talk enough: 🧬 Mitosis 🧬Transcription regulation and highlights how their coordination preserves cellular integrity
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9/ We further show that: Disrupting this timing → nucleolar fragmentation in interphase 👉 Mitotic transcription timing has consequences beyond mitosis
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8/ Importantly, this challenges the idea that transcription simply resumes passively as cells exit mitosis. Instead, reactivation is actively restrained and timed
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7/ This leads to: • early rRNA synthesis • premature recruitment of nucleolar components 👉Transcription turns ON too early
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6/ But here’s the unexpected part 👇 Loss of TTF2 triggers premature RNA Polymerase I activation during anaphase
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5/ As expected: Loss of TTF2 → retention of chromatin-associated transcripts in metaphase (mainly RNA Pol II–derived) ✔️ Consistent with its known role in transcriptional clearance
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4/ Using nascent RNA labeling polymerase-specific perturbations, we tracked transcription dynamics across mitosis in: • human embryonic stem cells • HeLa cells
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3/ We focused on TTF2, a factor known to remove RNA Polymerase II transcripts at mitotic entry. But what happens later—during transcriptional reactivation?
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2/ During mitosis, transcription is globally shut down. As cells exit mitosis, transcription must be reactivated—precisely and in the right order. How this timing is controlled remains poorly understood.
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🧵 Thread: What happens when transcription isn’t properly shut off during mitosis? Our new preprint explores just that 👇 biorxiv.org/content/10.64898…
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6/ 🧬 Check out the full preprint: biorxiv.org/content/10.64898…

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5/ This means that mitotic transcription isn’t just a passive consequence of cell cycle stage — it actively threatens genome stability when not properly regulated.
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4/ The result? When transcription isn’t cleared, sister chromatid resolution is impaired — a critical step needed to ensure faithful chromosome segregation in anaphase.
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3/ Importantly, we show that these defects arise because R-loops form when transcription persists during mitosis — and preventing transcription reverts the defects. That establishes a causal link.
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2/ Using TTF2 depletion to force nascent transcripts to persist on mitotic chromatin, we found that this abnormal retention leads to mitotic errors including abnormal chromosomes and bridges.
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1/ During mitosis, cells globally suppress transcription as chromosomes condense — a conserved hallmark of cell division. But what if this repression fails? 😮‍💨
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