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Alessandra Brambati @alebrambati.bsky.social · May 14

Agreed—it’s hard to quantify how often this occurs endogenously. Intron loss (Fig. 5), which captures this repair pathway at the endogenous level, reflects only a subset of mutagenic events. We assume that in most cases, the RT copies from pre-mRNA without leaving a detectable scar in the genome.

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Alessandra Brambati @alebrambati.bsky.social · May 12

@hinashah.bsky.social @agnelsfeir.bsky.social

Alessandra Brambati @alebrambati.bsky.social · May 12

Our study highlights RNA as a direct template for DNA repair, revealing RT-DSBR as a previously unrecognized and potentially mutagenic pathway. Huge thanks to the incredible team who made this work possible! (5/5)
🔗 www.nature.com/articles/s41...
#GenomeInstability #DNARepair #RNA #CRISPR #DSB

RNA transcripts serve as a template for double-strand break repair in human cells - Nature Communications

DNA double-stranded breaks threaten genome stability. Here, the authors show that transcript RNA serves as a repair template in human cells and identify Polζ as a key factor in RNA-templated DSB repai...

www.nature.com

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Alessandra Brambati @alebrambati.bsky.social · May 12

But does RT-DSBR leave a trace? Yes! Analysis of cancer genomes (MSK-IMPACT & PCAWG) revealed whole intron deletions (WIDs)—a mutational signature consistent with RNA being used as a template during repair. (4/5)

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Alessandra Brambati @alebrambati.bsky.social · May 12

CRISPR/Cas9 screens identified DNA polymerase ζ (Polζ) as essential for RT-DSBR. This translesion polymerase surprisingly acts as a reverse transcriptase—copying RNA into DNA right at break sites. (3/5)

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Alessandra Brambati @alebrambati.bsky.social · May 12

Using fluorescent and sequencing-based assays, we show that RNA-containing oligos and even mRNA can serve as templates for DSB repair in human cells. But which enzyme enables this RNA-templated process? (2/5)

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Alessandra Brambati @alebrambati.bsky.social · May 12

Excited to share our latest from my postdoc at @mskcancercenter.bsky.social in the Sfeir Lab, in collaboration with the Simon Powell Lab! We uncovered a novel genome repair mechanism in human cells: RNA-templated DNA double-strand break repair (RT-DSBR). (1/5)

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Reposted by Alessandra Brambati

Lopes_Lab @lopeslab.bsky.social · Mar 17

Exciting seminar series from Genome integrity italian Network (GiiN), chaired by myself and Raffaella Di Micco! Short talks (2x30’), at convenient time for EU/USA attendees. Big shots and raising stars in an expanding field. See flyers + link to receive email alerts. Please repost to your network!👇

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Reposted by Alessandra Brambati

Hoodlum 🇺🇸 @nothoodlum.bsky.social · Mar 3

A brilliant Banksy.

510 10K 39K

Alessandra Brambati @alebrambati.bsky.social · Feb 27

Huge thanks to the incredible team who made this work possible! 🙌

Check out the full preprint here: 🔗 doi.org/10.1101/2025...

#GenomeInstability #DNARepair #RNA #CRISPR #DSB #Genomics

@agnelsfeir.bsky.social @hinashah.bsky.social

doi.org

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Alessandra Brambati @alebrambati.bsky.social · Feb 27

🚀 This study highlights RNA as a direct template for genome repair, revealing RT-DSBR as a previously unrecognized repair pathway with potential mutagenic consequences in cancer. (7/)

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Alessandra Brambati @alebrambati.bsky.social · Feb 27

🔬But does RT-DSBR leave a footprint in the genome? YES! We analyzed cancer genome datasets (MSK-IMPACT & PCAWG) and found whole intron deletions (WIDs)—a mutational signature of RT-DSBR. (6/)

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Alessandra Brambati @alebrambati.bsky.social · Feb 27

🔥 CRISPR/Cas9 genetic screens identified DNA polymerase ζ (Polζ) as the key player in RT-DSBR. This translesion polymerase acts as a reverse transcriptase to copy RNA into DNA at break sites. (5/)

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Alessandra Brambati @alebrambati.bsky.social · Feb 27

🧬 Using fluorescent and sequencing-based assays, we show that RNA-containing oligos and mRNA can act as templates for DSB repair in human cells. But which enzyme facilitates this process? (4/)

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Alessandra Brambati @alebrambati.bsky.social · Feb 27

💥 DNA double-strand breaks (DSBs) are dangerous lesions that threaten genome integrity. While canonical repair pathways rely on DNA templates, we uncovered an alternative mechanism: RNA-templated DSB repair (RT-DSBR). (3/)

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Alessandra Brambati @alebrambati.bsky.social · Feb 27

Excited to share our latest work from my postdoc in the Sfeir Lab 🔬, in collaboration with the Simon Powell Lab! 🤝 This project was driven by an incredible team, including the amazing Manisha and superstar Hina! ✨ (2/)

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Alessandra Brambati @alebrambati.bsky.social · Feb 27

In the midst of all the NIH & NSF chaos, I want to take a moment to focus on some good news and talk about science! 🧬✨

🚨 New preprint alert! 🚨 doi.org/10.1101/2025...
🧵👇 (1/)

doi.org

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Alessandra Brambati @alebrambati.bsky.social · Feb 27

🧬 But does RT-DSBR leave a footprint in the genome? YES! We analyzed cancer genome datasets (MSK-IMPACT & PCAWG) and found whole intron deletions (WIDs)—a mutational signature of RT-DSBR. (6/)

Alessandra Brambati @alebrambati.bsky.social · Feb 27

🔥 CRISPR/Cas9 genetic screens identified DNA polymerase ζ (Polζ) as the key player in RT-DSBR. This translesion polymerase acts as a reverse transcriptase to copy RNA into DNA at break sites. (5/)

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Alessandra Brambati @alebrambati.bsky.social · Feb 27

🔬 Using fluorescent and sequencing-based assays, we show that RNA-containing oligos and mRNA can act as templates for DSB repair in human cells. But which enzyme facilitates this process? (4/)

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Alessandra Brambati @alebrambati.bsky.social · Feb 27

💥 DNA double-strand breaks (DSBs) are dangerous lesions that threaten genome integrity. While canonical repair pathways rely on DNA templates, we uncovered an alternative mechanism: RNA-templated DSB repair (RT-DSBR). (3/)

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Alessandra Brambati @alebrambati.bsky.social · Feb 27

Excited to share our latest work from my postdoc in the Sfeir Lab 🔬, in collaboration with the Simon Powell Lab! 🤝 This project was driven by an incredible team, including the amazing Manisha and superstar Hina! ✨ (2/)

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Alessandra Brambati @alebrambati.bsky.social · Feb 13

Very excited to be part of the Pharm family! This are confusing time, but I could not ask for a better Department to go through this. Now let’s focus on the science and we will be fine #admaiora

CU Department of Pharmacology @cupharmacology.bsky.social · Feb 12

This morning, our department hosted a welcome breakfast for our newest primary faculty member, Assistant Professor Ale Brambati, PhD. We’re thrilled to have her join us, and are so excited for what’s in store for the Brambati Lab!

@alebrambati.bsky.social #CUPharmacology #CUAnschutz

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Alessandra Brambati @alebrambati.bsky.social · Jan 28

I hear you, Helen, same here trying to prepare a grant. But we should get going. Science cannot stop!

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Alessandra Brambati @alebrambati.bsky.social · Dec 3

ahahah LOL, but also true!

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