The 16^th International Symposium on DNA Damage Response & Human Disease (isDDRHD-2025) was held in Qingdao, China (October 17-20, 2025). The meeting assembled approximately 250 participants and featured 39 invited speakers from many countries. Scientific sessions covered the topics of mechanistic understanding and conceptual advances in the areas of the DNA damage response (DDR), genome stability, replication stress and chromatin organization, structural elucidation of repair machineries, as well as RNA-related genome maintenance. Presentations also addressed how dysregulation of DDR pathways drives human pathologies, including cancer, neuropathies and gonad development, and discussed how to target DDR pathways for therapeutic development. In addition to oral presentations, poster sessions and discussions at café-breaks and off-sessions provided further information exchanges in a relaxed and friendly atmosphere, which promoted interactions between early-career and established scientists.

Modification with UFM1 (UFMylation) has recently emerged as a versatile signaling system regulating diverse cellular processes, from endoplasmic reticulum homeostasis to genome stability. Recent studies have expanded this landscape by revealing a direct role of UFMylation in the core machinery of DNA replication. Specifically, UFMylation of MCM5 is required for optimal activation of the CDC45–MCM–GINS (CMG) helicase, the molecular engine that governs origin firing and drives replication fork progression. This discovery introduces a previously unrecognized regulatory layer into the DNA replication program and positions UFMylation as an important coordinator of genome duplication, whose disruption provides a mechanistic explanation for developmental disorders such as microcephalic primordial dwarfism (MPD), while more subtle or progressive dysregulation may have important implications for genome stability across ageing and cancer.