Seminar | Matinée de l’Intégrité du Génome
Seminar « Functional Genomics of Microsatellite Unstable Tumors and Therapeutic Target Discovery » by Gabriele Picco (Sanger Institute) 11:00 05/12/2025 at Roger Monier.
Seminar « Functional Genomics of Microsatellite Unstable Tumors and Therapeutic Target Discovery » by Gabriele Picco (Sanger Institute) 11:00 05/12/2025 at Roger Monier.
The S. Gad group of Ishchenko team leads this work on a novel genetic condition linked to Hereditary renal cell carcinomas (RCC). The team identified a frameshift mutation in NBR1, a gene involved in autophagy. Their findings suggest NBR1 as a potential new RCC predisposition gene, pending further validation.
OK-seq is a technique that sequences strand-specific Okazaki fragments to map replication initiation and termination in mammalian genomes. It quantifies fork directionality, revealing replication dynamics at high resolution. N. Petryk team contributes to this work to provide detailed protocols for OK-seq in human cells and yeast, alongside bioinformatics pipelines.
The ATR/Chk1 pathway regulates cell cycle progression, especially during DNA damage by inducing arrest for repair. Beyond damage response, Chk1 prevents premature mitosis during normal S phase, maintaining genome integrity. The Gavet team developed a FRET-based reporter to monitor Chk1 activity in live single cells with high sensitivity. This tool reveals Chk1 dynamics during normal and stressed conditions.
« DNA adducting carcinogens exacerbate APOBEC mutagenesis and carcinogenesis »
Reuben Harris (UT San Antonio, US)
01/10/2025 at 11h
Salle Pierre Denoix (15th Floor Gustave Roussy main builiding)
The 7th German-French DNA repair meeting will be held this November 5th-7th in Paris. The unit is this time involved as hosting/organizing committee of the meeting. We will wellcome you soon!
The Kannouche team participate in this article presenting the results of the phase 2 ICARUS-BREAST01 study. The study showed a 53.5% response rate to HER3-DXd (an antibody–drug conjugate) in HR+HER2− metastatic breast cancer after CDK4/6 inhibitor and chemotherapy treatment.
This is a collaborative effort of the Kannouche and Mazon/LeCam teams of the unit. DNA lesions during S phase challenge genome stability, managed by DNA damage tolerance (DDT) via TLS polymerases or recombination. Using electron microscopy, we show TLS polymerase η acts at replication forks to prevent gaps after UV damage. We outline a timeline of UV damage tolerance highlighting polη’s crucial role in DNA synthesis continuity.
The Gavet team developed a FRET-based sensor to specifically monitor Chk1 activity during replication stress (RS).
Basal Chk1 activity during S phase depends on replication origin firing, with RS triggering stepwise Chk1 over-activation that delays S-phase.
Chk1 is inactivated upon replication completion but reactivates in some G2 cells to block premature mitosis.
Cells can override active Chk1 signaling to enter mitosis, revealing checkpoint adaptation.
Beatrice Rondinelli co-authors a study revealing that pediatric high-grade gliomas (pHGG) with H3.3 mutations exhibit aberrant DNA repair promoting genome instability. Their findings suggest new therapeutic targets for treating H3.3 mutant pHGG.