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.
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.
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.
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.
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).
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.
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.
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.
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.
Lead by the postdocs of Mazon’s team, I. Talhaoui and M. Bernal, the article describes the regulation of Yen1 resolvase protein pools to control mitotic crossove formation during DSB repair.