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Pedro Ortega

@pedroorteg.bsky.social

255 followers 347 following 16 posts

Postdoctoral researcher at @CABIMER. Former researcher at @UCIrvine and @unisevilla. Cellular Stress Signaling and Poly(ADP-ribose) biology. scholar.google.com/citations?user=U…

Posts Replies Media

Pedro Ortega @pedroorteg.bsky.social · 29/04/2025

We describe how to perform Oligo-seq, a new method to map DNA motifs targeted by base editors. Validated with APOBEC3A and APOBEC3B, but adaptable to AID, CRISPR-Cas9, and more. 🧬 Full protocol 👉 www.sciencedirect.com/science/arti... Thanks to @buissonlab.bsky.social at @ucirvine.bsky.social!

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Pedro Ortega @pedroorteg.bsky.social · 07/04/2025

Glad to see our PACT preprint published in @naturecomms.bsky.social! "Cooperative role of PACT and ADAR1 in preventing aberrant PKR activation by self-derived double-stranded RNA" Another step forward in understanding innate immunity. @buissonlab.bsky.social 🔗 www.nature.com/articles/s41...

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Pedro Ortega @pedroorteg.bsky.social · 28/11/2024

Check out our new pre-print! 🦠🧬🦠🧬🦠 We used a FACS-based CRISPR-Cas9 screening method that exploits translation levels as a readout and identified PACT as a key inhibitor (not an activator!) of PKR during RNA viral infections. @buissonlab.bsky.social www.biorxiv.org/content/10.1...

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Pedro Ortega @pedroorteg.bsky.social · 16/11/2024

Together, these findings highlight how ATR inhibition leads to replication catastrophe and explain why ATR inhibitor-treated cells are highly sensitive to PARP inhibition.

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Pedro Ortega @pedroorteg.bsky.social · 16/11/2024

Using MMS, MNNG, and H2O2 as alternative sources of abasic sites, we further demonstrate that APE1 cleavage is the key step for PARP1 activation, regardless of how abasic sites form in cells.

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Pedro Ortega @pedroorteg.bsky.social · 16/11/2024

The APOBEC3B-UNG2-APE1-driven fork breakage activates and traps PARP1 on DNA. Although PARP1 activation recruits the repair factor XRCC1, toxic PARP1 trapping, further enhanced by PARP inhibition, sensitizes cells to ATR inhibitors.

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Pedro Ortega @pedroorteg.bsky.social · 16/11/2024

Mechanistically, we demonstrate that APOBEC3B deaminates cytosines to uracils on ssDNA, initiating a chain of events where UNG2 removes the uracils, creating abasic sites that APE1 cleaves. This process results in fork breakage and PARP1 hyperactivation.

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Pedro Ortega @pedroorteg.bsky.social · 16/11/2024

ATR inhibition triggers a surge in origin firing, depleting the pool of RPA and leaving ssDNA at replication forks unprotected, leading to replication catastrophe. Here, we demonstrate that APOBEC3B targets ssDNA, initiating a cascade of events that culminate in PARP1 activation.

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