H263A and SCAN1/H493R mutant TDP1 block TOP1-induced double-strand break repair during gene transcription in quiescent cells and promote cell death

Muy contentos de que nuestro último trabajo haya sido elegido como artículo del mes de febrero por la @sebbm.bsky.social @ibis-investigacion.bsky.social

Terrific work of Diana Rubio-Contreras and Daniel Hidalgo-García

These results support the potential role of TOP1-induced DSBs as a main contributor to certain hereditary neurological syndromes.

We demonstrate that TDP1 catalytic mutations H263A and H493R (SCAN1), promote TOP1 cleavage complexes and TDP1-DNA covalent complexes respectively generating persistent TOP1-induced DSBs on quiescent cells. TDP1 mutants result in increased genome instability and reduced cell viability.

H263A and SCAN1/H493R mutant TDP1 block TOP1-induced double-strand break repair during gene transcription in quiescent cells and promote cell death Cell Death & Disease - H263A and SCAN1/H493R mutant TDP1 block TOP1-induced double-strand break repair during gene transcription in quiescent cells and promote cell death

New manuscript from the lab on @cddpress " H263A and SCAN1/H493R mutant TDP1 block TOP1-induced Double-Strand Break Repair during gene transcription in quiescent cells and promote cell death". rdcu.be/eSxtG @ibis-investigacion.bsky.social @unisevilla.bsky.social

Finally published! Our work on how the #CircadianClock controls DNA repair. This has direct implications for cancer treatment: #Chronotherapy.
@CABIMER @UniSevilla

rdcu.be/eSwxl

Uncoupling of nutrient sensing and cell size control by specific defects in ceramide structure Ceramides are essential structural lipids whose chemical diversity arises from variations in acyl-chain length and sphingoid base modifications, yet how these structural features couple metabolic stat...

Our new preprint is out! Great work from Nacho Quesada during his TFG/TFM in our lab, where we found some interesting data on ceramide structure and TORC2 signaling in response to nutrients. Thanks to Anita and Maria Alcaide-Gavilan for helping!
www.biorxiv.org/content/10.1...

Excited to see our research published!! 🎉

Amazing project in @fgh-lab.bsky.social at @ibis-investigacion.bsky.social

"H263A and SCAN1/H493R mutant TDP1 block TOP1-induced double-strand break repair during gene transcription in quiescent cells and promote cell death"

www.nature.com/articles/s41...

A comprehensive genetic catalog of human double-strand break repair The analysis of DNA sequence outcomes provides molecular insights into double-strand break (DSB) repair mechanisms. Using parallel in-pool profiling of Cas9-induced insertions and deletions (indels) w...

Kickstarting our Bluesky🦋 account with great news!
Our REPAIRome study finally out today in
@science.org
www.science.org/doi/10.1126/...

DNA2 enables growth by restricting recombination-restarted replication - Nature DNA2 suppresses recombination-restarted replication and checkpoint activation at stalled forks, and its loss triggers recombination-dependent synthesis, checkpoint signalling and cell-cycle exit, high...

#New-Paper Rass laboratory reveal DNA2 to be a gatekeeper to homologous recombination at stalled DNA replication forks, rrequired to stave off cellular senescence. Their findings provide a molecular explanation for the association of DNA2 with primordial dwarfism and cancer.

doi.org/10.1038/s415...

👉EWS::FLI1 modulates R-loop metabolism via DHX9, driving increased vulnerability to TOP1-targeting agents.
👉Targeting TOP1 in EWS cells destabilizes the genome and provokes strong replication stress and cell death in EwS cells and tumors

Grateful to all collaborators who made this work possible!

EWS::FLI1-DHX9 interaction promotes Ewing sarcoma sensitivity to DNA topoisomerase 1 poisons by altering R-loop metabolism - Oncogene Oncogene - EWS::FLI1-DHX9 interaction promotes Ewing sarcoma sensitivity to DNA topoisomerase 1 poisons by altering R-loop metabolism

Our latest study is now online! A great collaboration between the @fgh-lab.bsky.social and @enriquedealava.bsky.social Labs, driven by the outstanding work of J. Olmedo-Pelayo at @ibis-investigacion.bsky.social Check it out!

PLAMseq enables the proteo-genomic characterization of chromatin-associated proteins and protein interactions in a single experimental workflow. Chromatin Immunoprecipitation (ChIP) and Co-Immunoprecipitation (CoIP) assays are the most common approaches to characterize the genomic localization and protein interactors, respectively, for a prote...

New preprint from the Lab at @cabimer.bsky.social. We present PLAMseq, using TurboID to do like ChIPseq and proximity proteomics in the same protocol with extra powers like mapping protein interactions in the genome.

www.biorxiv.org/content/10.1...