The team is based at the Centre de Biologie Intégrative (CBI, Toulouse), a large-scale research hub bringing together nearly 400 people working on diverse topics. The CBI is located on the campus of Université Paul Sabatier. https://cbi-toulouse.fr/

This project is funded by an ANR JCJC and focuses on the repair of DNA breaks with non-canonical ends, particularly 5'OH ends. DNA breaks account for approximately 75% of all DNA lesions and often have so-called "dirty" ends (lacking 5' phosphate or 3' hydroxyl groups), with atypical chemical modifications (e.g., 5'hydroxyl, 5'aldehyde, 3'phosphate, etc.). These ends must be processed or repaired to restore DNA integrity, but this process increases the risk of errors, thereby promoting genomic instability. However, the way these "dirty" breaks contribute to this instability remains poorly understood, despite its critical importance for assessing their impact on human diseases such as aging, neurodegenerative diseases, or cancer.

Among the most frequent breaks are those with 5'hydroxyl (5'OH) ends. These breaks are caused by exogenous sources (e.g., irradiation, chemotherapeutic agents like camptothecin) or endogenous sources (e.g., cellular metabolism via reactive oxygen species or the activity of Topoisomerase 1). This PhD project aims to answer a key question: How do 5'OH breaks contribute to genomic instability? This will be investigated using various genomic approaches.

The team is based at the Centre de Biologie Intégrative (CBI, Toulouse), a large-scale research hub bringing together nearly 400 people working on diverse topics. The CBI is located on the campus of Université Paul Sabatier. https://cbi-toulouse.fr/

This project is funded by an ANR JCJC and focuses on the repair of DNA breaks with non-canonical ends, particularly 5'OH ends. DNA breaks account for approximately 75% of all DNA lesions and often have so-called "dirty" ends (lacking 5' phosphate or 3' hydroxyl groups), with atypical chemical modifications (e.g., 5'hydroxyl, 5'aldehyde, 3'phosphate, etc.). These ends must be processed or repaired to restore DNA integrity, but this process increases the risk of errors, thereby promoting genomic instability. However, the way these "dirty" breaks contribute to this instability remains poorly understood, despite its critical importance for assessing their impact on human diseases such as aging, neurodegenerative diseases, or cancer.

Among the most frequent breaks are those with 5'hydroxyl (5'OH) ends. These breaks are caused by exogenous sources (e.g., irradiation, chemotherapeutic agents like camptothecin) or endogenous sources (e.g., cellular metabolism via reactive oxygen species or the activity of Topoisomerase 1). This PhD project aims to answer a key question: How do 5'OH breaks contribute to genomic instability? This will be investigated using various genomic approaches.