Raphaël Ceccaldi
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View article: Uracil processing by SMUG1 in the absence of UNG triggers homologous recombination and selectively kills BRCA1/2-deficient tumors
Uracil processing by SMUG1 in the absence of UNG triggers homologous recombination and selectively kills BRCA1/2-deficient tumors Open
Resistance to poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis) is the major obstacle to their effectiveness in the treatment of homologous recombination (HR)-deficient (HRD) tumors. Hence, developing alternative treatments for HRD t…
View article: DNA damage induces nuclear envelope rupture through ATR-mediated phosphorylation of lamin A/C
DNA damage induces nuclear envelope rupture through ATR-mediated phosphorylation of lamin A/C Open
The integrity of the nuclear envelope (NE) is essential for maintaining the structural stability of the nucleus. Rupture of the NE has been frequently observed in cancer cells, especially in the context of mechanical challenges, such as ph…
View article: Polθ is phosphorylated by PLK1 to repair double-strand breaks in mitosis
Polθ is phosphorylated by PLK1 to repair double-strand breaks in mitosis Open
DNA double-strand breaks (DSBs) are deleterious lesions that challenge genome integrity. To mitigate this threat, human cells rely on the activity of multiple DNA repair machineries that are tightly regulated throughout the cell cycle 1 . …
View article: A clickable melphalan for monitoring DNA interstrand crosslink accumulation and detecting ICL repair defects in Fanconi anemia patient cells
A clickable melphalan for monitoring DNA interstrand crosslink accumulation and detecting ICL repair defects in Fanconi anemia patient cells Open
Fanconi anemia (FA) is a genetic disorder associated with developmental defects, bone marrow failure and cancer. The FA pathway is crucial for the repair of DNA interstrand crosslinks (ICLs). In this study, we have developed and characteri…
View article: Polθ is phosphorylated by Polo-like kinase 1 (PLK1) to enable repair of DNA double strand breaks in mitosis
Polθ is phosphorylated by Polo-like kinase 1 (PLK1) to enable repair of DNA double strand breaks in mitosis Open
DNA double strand breaks (DSBs) are deleterious lesions that challenge genome integrity. To mitigate this threat, human cells rely on the activity of multiple DNA repair machineries that are tightly regulated throughout the cell cycle 1 . …
View article: Nuclear NAD<sup>+</sup> homeostasis is essential for naive and chemoresistant <i>BRCA1/2</i>-deficient tumor survival
Nuclear NAD<sup>+</sup> homeostasis is essential for naive and chemoresistant <i>BRCA1/2</i>-deficient tumor survival Open
Resistance to PARP inhibitors (PARPi) is emerging as the major obstacle to their effectiveness for the treatment of BRCA1/2 -mutated, also referred as homologous recombination (HR)-deficient, tumors (HRD). Over the years, mechanistic studi…
View article: Polymerase Theta Inhibition Kills Homologous Recombination Deficient Tumors
Polymerase Theta Inhibition Kills Homologous Recombination Deficient Tumors Open
PARP inhibitors (PARPi) have become a new line of therapy for Homologous Recombination (HR)-deficient cancers. However, resistance to PARPi has emerged as a major clinical problem. DNA polymerase theta (POLθ) is synthetic lethal with HR an…
View article: Biallelic inactivation of REV7 is associated with Fanconi anemia
Biallelic inactivation of REV7 is associated with Fanconi anemia Open
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View article: Biallelic inactivation of REV7 is associated with Fanconi anemia
Biallelic inactivation of REV7 is associated with Fanconi anemia Open
Fanconi anemia (FA) is a recessive genetic disease characterized by congenital abnormalities, chromosome instability, progressive bone marrow failure (BMF), and a strong predisposition to cancer. Twenty FA genes have been identified, and t…
View article: Homologous Recombination Deficiency: Exploiting the Fundamental Vulnerability of Ovarian Cancer
Homologous Recombination Deficiency: Exploiting the Fundamental Vulnerability of Ovarian Cancer Open
Approximately 50% of epithelial ovarian cancers (EOC) exhibit defective DNA repair via homologous recombination (HR) due to genetic and epigenetic alterations of HR pathway genes. Defective HR is an important therapeutic target in EOC as e…
View article: A Unique Subset of Epithelial Ovarian Cancers with Platinum Sensitivity and PARP Inhibitor Resistance
A Unique Subset of Epithelial Ovarian Cancers with Platinum Sensitivity and PARP Inhibitor Resistance Open
Platinum and PARP inhibitor (PARPi) sensitivity commonly coexist in epithelial ovarian cancer (EOC) due to the high prevalence of alterations in the homologous recombination (HR) DNA repair pathway that confer sensitivity to both drugs. In…