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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).

Monitoring and quantifying replication fork dynamics with high-throughput methods

The N. Petryk lab highlights in this work advances in quantitative technologies that deepen understanding of chromosome replication beyond DNA duplication.
Their work reveals how replication forks manage chromatin assembly and epigenetic inheritance during cell division.
They also elucidate mechanisms of replication-coupled chromatin assembly and epigenome maintenance.

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.

Contribution of p53-dependent and -independent mechanisms to upregulation of p21 in Fanconi anemia

F. Rosselli’s team shows in this article how abnormal p21 expression in Fanconi anemia (FA) contributes to bone marrow failure and genetic instability.
This upregulation depends not only on p53 but also on MITF and its interaction with NPM1.
In FA cells, p21 accumulates on chromatin, binds PCNA, and prolongs S-phase, leading to replication stress.
Depleting p21 restores replication timing and reduces instability.
ROS levels in FA cells promote p21-PCNA association, further impairing DNA replication.

SUMO-mediated recruitment allows timely function of the Yen1 nuclease in mitotic cells

In this article, the Mazon’s team PhD student H. Dorison goes deeper in the understanding of the SUMO-mediated regulation of the resolvase Yen1 in mitotic cells.