derianolab - Bluesky Statics

👏 Amazing work by François Dossin and collaborators, including the teams of @icrlordlab.bsky.social and @lopeslab.bsky.social !

16.01.2026 11:50 — 👍 2 🔁 0 💬 0 📌 0

✅ FANCM–RMI1/2 acts as an opposing modulator of genome integrity and cell fitness following acute loss of BRCA1 or BRCA2, highlighting FANCM as a new determinant of cell vulnerability and therapeutic response.

16.01.2026 11:48 — 👍 2 🔁 0 💬 0 📌 0

✅ Hundreds of genes show shared, distinct, or opposing effects in BRCA1 vs BRCA2 deficient cells, with direct implications for prevention and therapy based on BRCA mutation status.

16.01.2026 11:48 — 👍 2 🔁 1 💬 0 📌 0

The FANCM-RMI1/2 complex promotes genomic instability and PARP inhibitor sensitivity in BRCA2-deficicient cells. Cancer cells lacking BRCA1 or BRCA2 must adapt to survive and proliferate despite defective DNA repair and high genomic instability. Restoration of homologous recombination (HR) through loss of DNA end protection rescues growth defects and promotes PARP inhibitor (PARPi) resistance in BRCA1-deficient cells; however, the genetic basis of adaptation to BRCA2 loss remains largely unexplored. To delineate BRCA1- and BRCA2-specific adaptation trajectories, we established a fully isogenic screening platform in mouse embryonic stem cells engineered for acute depletion of either protein. This approach uncovered hundreds of genes with shared, distinct, or even opposing effects between the two BRCA-deficiency states. We identified FANCM and its interacting partners RMI1/2, CENPS/MHF1, CENPX/MHF2, and FAAP24 as essential in BRCA1-deficient cells but toxic in BRCA2- deficient contexts. Loss of FANCM in BRCA2-deficient cells alleviated genomic instability and proliferation defects by preventing RMI1/2-dependent replication fork degradation, without rescuing HR. Moreover, we show that the FANCM-RMI1/2 complex drives PARPi sensitivity in both mouse and human BRCA2-deficient cells, in contrast to the 53BP1-SHLD-CST axis in BRCA1-deficient cells. These findings reveal distinct adaptation routes to BRCA1 and BRCA2 loss and establish FANCM as a determinant of BRCA2-specific vulnerability and therapeutic response, with direct implications for tailoring prevention and therapy according to BRCA mutation status. ### Competing Interest Statement C.J.L. makes the following disclosures: receives and/or has received research funding from: AstraZeneca, Merck KGaA, Artios, Neophore, FoRx. Received consultancy, SAB membership or honoraria payments from: FoRx, Syncona, Sun Pharma, Gerson Lehrman Group, Merck KGaA, Vertex, AstraZeneca, Tango Therapeutics, 3rd Rock, Ono Pharma, Artios, Abingworth, Tesselate, Dark Blue Therapeutics, Pontifax, Astex, Neophore, Glaxo Smith Kline, Dawn Bioventures, Blacksmith Medicines, ForEx, Ariceum. Has stock in: Tango, Ovibio, Hysplex, Tesselate, Ariceum. C.J.L. is also a named inventor on patents describing the use of DNA repair inhibitors and stands to gain from their development and use as part of the ICR Rewards to Inventors scheme and also reports benefits from this scheme associated with patents for PARP inhibitors paid into CJL's personal account and research accounts at the Institute of Cancer Research. 020

🚨 New preprints from the lab!

www.biorxiv.org/content/10.6...

How do cells adapt when BRCA1 or BRCA2 are suddenly lost? 🧬

We built a genome scale genetic adaptation map to find out.

#BRCA #CRISPR #DNARepair #Cancer

16.01.2026 11:44 — 👍 3 🔁 1 💬 4 📌 0

2026 DNA Damage, Mutation and Cancer Conference GRC The 2026 Gordon Research Conference on DNA Damage, Mutation and Cancer will be held in Ventura, California. Apply today to reserve your spot.

Check out the GRC for DNA damage and Cancer! Join us in Summy California for a week of DNA repair and Cancer! www.grc.org/dna-damage-m...

15.01.2026 00:08 — 👍 7 🔁 7 💬 0 📌 0

Polymerase theta repairs persistent G1-induced DNA breaks in S-phase during class switch recombination Nature Communications - NHEJ is the primary repair pathway during class switch recombination. Here the authors show that in absence of NHEJ, Pol θ repairs persistent G1-induced breaks in...

🚨 Check out our latest article! 🚨
Spoiler: when NHEJ is out, polymerase theta steps in to fix persistent G1-phase breaks during the next S phase — not in mitosis! And for our fellow B cell fans, we explore how Pol θ contributes to immunoglobulin class switching.

@natcomms.nature.com
rdcu.be/eRTSe

26.11.2025 15:50 — 👍 5 🔁 4 💬 0 📌 1

Senataxin promotes recombination fidelity during antigen receptor gene diversification A CRISPR screen reveals a protective role for the RNA/DNA helicase senataxin during V(D)J recombination.

Our lab’s newest publication is now online! Senataxin promotes recombination fidelity during antigen receptor gene diversification | Science Signaling www.science.org/doi/10.1126/...

15.10.2025 05:26 — 👍 4 🔁 1 💬 0 📌 0

RAD51-mediated homologous recombination is a pro-tumour driver pathway - Oncogene Oncogene - RAD51-mediated homologous recombination is a pro-tumour driver pathway

Plot twist: homologous recombination actually promotes the development of cancer!

This discussion has been started in the hope that it will be useful, see the link:

doi.org/10.1038/s413...

24.09.2025 14:50 — 👍 5 🔁 2 💬 0 📌 1

I am looking forward to my visit and to sharing some of our recent work with QBI colleagues!

01.08.2025 15:41 — 👍 1 🔁 0 💬 0 📌 0

Genome rearrangements induced by the stimulation of end-joining of DNA double strand breaks through multiple phosphorylation of MRE11 by the kinase PKB/AKT1 Abstract. Genetic instability is a major hazard threatening the fate of cells and ultimately of organisms. DNA double-strand break (DSB) is a highly toxic

The hyper-activation of DNA double-strand break repair by the AKT1/PKB oncogene generates genetic instability.
(A new role for the oncogene AKT1: the phosphorylation of MRE11).
academic.oup.com/nar/article-...

11.06.2025 12:24 — 👍 2 🔁 2 💬 0 📌 0

CST Is Epistatic With Shieldin to Limit DNA Double‐Strand Break End Resection and Promote Repair During Igh Class Switch Recombination Here we show that CST and SHLD are required for CSR, while SHLD1-CTC1 interaction via the SHLD1 LDLP motif is dispensable. Mechanistically, we show that CTC1 and SHLD1 are epistatic during CSR, preve...

New publication from the lab. CST Is Epistatic With Shieldin to Limit DNA Double‐Strand Break End Resection and Promote Repair During Igh Class Switch Recombination - Lescale - 2025 - European Journal of Immunology - Wiley Online Library onlinelibrary.wiley.com/doi/full/10....

03.04.2025 19:24 — 👍 3 🔁 0 💬 0 📌 0

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