Rémi Buisson

Thanks for the great description of our recent study!

Thanks Debbie!!

Many thanks to @pedroorteg.bsky.social for leading this work, and to @johnmaciejowski.bsky.social and the Abby Green Lab for their contributions to the story.

Mechanism of DNA replication fork breakage and PARP1 hyperactivation during replication catastrophe Upon ATR inhibition, APOBEC3B targets unprotected single-stranded DNA at replication forks, leading to fork breakage.

Today, we report that APOBEC3B targets unprotected single-stranded DNA at replication forks upon ATR inhibition, triggering a reaction cascade involving UNG2 and APE1 that leads to fork collapse and hyperactivation of PARP1, causing replication catastrophe.
www.science.org/doi/10.1126/...

Transcription stress causes an inflammatory response via release of IL-1α Nature Structural & Molecular Biology - DNA damage can be sensed as a danger signal by the innate immune system. Bournique et al. show that the transcription stress caused by DNA lesions can...

A beautiful News & Views by @unterholznerlab.bsky.social highlighting our latest paper in @natsmb.nature.com, where we show that transcription stress triggers an inflammatory response through the release of IL-1α. rdcu.be/ehkTV

Thank you so much for this beautiful review of our paper!!

Thanks!!

Cooperative role of PACT and ADAR1 in preventing aberrant PKR activation by self-derived double-stranded RNA - Nature Communications Uncontrolled activation of PKR by endogenous double-stranded RNA (dsRNA) is detrimental to cells, as it leads to global translational shutdown. Here, we show that PACT and ADAR1 establish a threshold ...

Today, we report our new study demonstrating that PACT functions as an inhibitor rather than an activator of PKR, and works together with ADAR1 to suppress aberrant activation of PKR by self-derived double-stranded RNA. www.nature.com/articles/s41...

UCI Anteaters standing up for science today!

Very sad to read about the science funding situation in the US at the moment. I am waiting for some funding decisions in the coming weeks, but I will likely have opening(s) in my lab in Switzerland in the coming weeks (PhD student/postdoc). As a PhD candidate, you need to have a Master's degree.

Happy to report the 2025/05 NIH Biochemical and Cellular Oncogenesis (BCO) study section meeting has been rescheduled for late April. Just FYI.

The 2025/05 NIH Biochemical and Cellular Oncogenesis (BCO) study section meeting that was supposed to happen tomorrow has been rescheduled to a later date, to be determined. Just FYI for folks wondering. This is so disheartening.

So frustrating! For both reviewers and applicants…. So much work for nothing….

ATM and IRAK1 orchestrate two distinct mechanisms of NF-κB activation in response to DNA damage Nature Structural & Molecular Biology - In this study, the authors show that DNA-damage-mediated transcriptional stress induces NF-κB through IRAK1, allowing damaged cells with impaired...

Free access to the paper: rdcu.be/d5pue

Our findings provide an alternative mechanism for damaged cells with impaired transcription to initiate an inflammatory response without relying on their own gene expression, a necessary step that injured cells depend on during canonical innate immune responses.

ATM and IRAK1 orchestrate two distinct mechanisms of NF-κB activation in response to DNA damage - Nature Structural & Molecular Biology In this study, the authors show that DNA-damage-mediated transcriptional stress induces NF-κB through IRAK1, allowing damaged cells with impaired transcription to initiate an inflammatory response wit...

Today @naturesmb.bsky.social 🥳, we report that the activation of NF-κB after DNA damage can occur through two distinct mechanisms. While ATM triggers NF-κB activation after DSBs, we found that IRAK1 specifically induces NF-κB in response to DNA damage causing transcriptional stress.

Thank you very much! I am glad you liked our story!

Congratulation 🥳

Our detailed protocol revealing our secret to performing perfect in vitro APOBEC deaminase reactions on DNA substrates at near-nucleotide resolution. authors.elsevier.com/a/1kDyIHRzCU...

Félicitation !!!🥳

We propose that both PACT and ADAR1 act as essential barriers against PKR, creating a threshold of tolerable levels to endogenous dsRNA in cells without activating PKR-mediated translation shutdown and cell death.

Simultaneous deletion of PACT and ADAR1 results in synthetic lethality, which can be fully rescued in PKR-deficient cells. This suggests PACT cooperates with ADAR1 to suppress PKR activation from self-dsRNAs in uninfected cells.

Our Alphafold 3 modeling analysis of PACT reveals the formation of a dimer that surrounds dsRNA, blocking access to both sides of the dsRNA and thereby preventing PKR activation.

We find that cells deficient for PACT hyperactivate PKR in response to several different RNA viruses, raising the question of why cells need to limit PKR activity? We show that it is critical to prevent PKR activation from self-dsRNA.

Cooperative Role of PACT and ADAR1 in Preventing Aberrant PKR Activation by Self-Derived Double-Stranded RNA Double-stranded RNAs (dsRNAs) produced during viral infections are recognized by the innate immune sensor protein kinase R (PKR), triggering a host translation shutoff that inhibits viral replication ...

New Lab Preprint!🥳 Using CRISPR-Translate, a genome-wide CRISPR-Cas9 knockout screening method developed by the lab exploiting translation levels as a readout, we reveal that PACT is an inhibitor of PKR and not an activator during RNA viral infections. www.biorxiv.org/content/10.1...

It was nice seeing you!! And to remember what winter feels like 🥶

Thank you very much!!

Thanks to @pedroorteg.bsky.social orteg for driving this project

Our findings uncover the mechanisms behind replication fork collapse during replication catastrophe and show that APOBEC3B drives cell sensitivity caused by ATR and PARP inhibitors.