Workshop DNA–Protein Crosslinks: Mechanisms and Links to Rare Genetic Disorders
Presentación y objetivos
The interaction of proteins with DNA during replication, transcription, and repair is precisely required to faithful transmission of genetic information. While transient protein–DNA interactions are essential for normal chromatin function, the aberrant stabilization of these protein–DNA contacts can culminate in the formation of covalent DNA-protein crosslinks (DPCs). These bulky, helix-distorting adducts arise through diverse chemical mechanisms — from the attack of reactive aldehydes and oxidative species to the abortive catalysis of topoisomerases and other DNA-processing enzymes — thus threatening genomic integrity at every stage of the cell cycle. Understanding how cells detect, tolerate, and ultimately resolve DPCs has emerged as one of the most exciting frontiers in genome maintenance research. Recent years have witnessed the discovery of dedicated DPC proteases, the unveiling of replication-coupled repair mechanisms, and the identification of specialized damage tolerance pathways at stalled forks. The pathological consequences of defective DPC repair have just started to emerge and are underscored by human syndromes characterized by premature aging and cancer predisposition linked to mutations in DPC repair factors.
This workshop brings together top-class researchers who have pioneered several aspects of DPC biology, working across DNA replication, repair, chromatin biology, structural biology, and cancer genomics to share cutting-edge discoveries and forge new collaborations. Whether your focus lies on mechanistic biochemistry, animal models of genomic instability, or the clinical implications of DPC accumulation in aging and cancer, this meeting offers a unique and timely forum to advance our collective understanding of this critical — and still incompletely understood — class of DNA damage.
