Archives des News - Page 2 sur 3

Changes in the architecture and abundance of replication intermediates at UV-stalled replication forks in human cells

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.

Effect of Mismatch repair deficiency on metastasis occurrence in a syngeneic mouse model

This work, led by P. Laplante in Kannouche’s team, shows how mismatch repair deficiency causes high mutation rates and microsatellite instability (MSI-H), linked to immune infiltration and immunotherapy response.
A syngeneic MSI breast cancer mouse model with Msh2 knockout showed reduced metastasis and immune gene enrichment. Aggressive hybrid epithelial-mesenchymal signatures appeared only in metastatic MSI-H tumors. Immature myeloid cells at tumor sites suggest unique immune responses beyond T-cell activation in MMR deficiency.

Retraite de l’unité 16 Octobre 2025

La retraite de l’unité aura lieu le 16 Octobre 2025 à la cité U (Fondation Deutsch de la Meurthe). RDV à 8:45!

Fondation Deutsch de la Meurthe au CIUP (RER cité U).

Attention ! :

– L’Accès Piéton se fera par le 37 Boulevard Jourdan, 75014 PARIS
– L’Accès voiture se fera par les 27/29/31 Boulevard Jourdan 75014 PARIS

Chk1 dynamics in G2 phase upon replication stress predict daughter cell outcome

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.

Aberrant DNA repair reveals a vulnerability in histone H3.3-mutant brain tumors

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.

Genomic mutation landscape of skin cancers from DNA repair-deficient xeroderma pigmentosum patients

This article is a collaboration of the Kannouche team with the Gustave Roussy’s team of S. Nikolaev. Xeroderma pigmentosum (XP) is caused by mutations in NER genes or DNA polymerase η, leading to a greatly increased skin cancer risk.
Analysis of 38 XP skin cancer genomes reveals that NER activity drives mutation rate variability and that transcription-coupled NER reduces intergenic mutations.
The findings clarify the genetic basis of skin cancer risk in XP.

DCLRE1B/Apollo germline mutations associated with renal cell carcinoma impair telomere protection

C. Bories, a PhD student under F. Renaud supervision in the Ishchenko team, leads the study identifying germline Apollo gene variants in hereditary renal cell carcinoma (RCC). Their findings implicate Apollo mutations in genomic instability and potential renal oncogenesis.

Human RAD52 stimulates the RAD51-mediated homology search

In a work led by A. Muhammad, a PhD student under P. Dupaigne supervision in the team, we show that RAD52 forms shorter, efficient RAD51-RAD52 mixed filaments that enhance synaptic complex formation and D-loops. This study provides new molecular insights into the formation and regulation of presynaptic and synaptic intermediates by BRCA2 and RAD52 during human HR.

Abasic site-peptide cross-links are blocking lesions repaired by AP endonucleases

A. Ishchenko participates in this study of the fate of the DNA-protein crosslinks generated by the activity of AP endonucleases using two in vitro models of APPXLs (AP-peptide cross-links).

Restriction of Ku translocation protects telomere ends

In a collaborative effort, the Mazon/Le Cam team used Cryo-EM to reveal how Rap1 inhibits Ku’s NHEJ activity at telomeres.
Rap1 binds near DNA breaks, blocking Ku’s inward translocation without displacing it. The study uncovers how Ku switches from repair-promoting to protective roles at telomeres.