Ongoing repair of migration-coupled DNA damage allows stem cells to reach wound sites

Abstract The impact of mechanical stress during cell migration may be a previously unappreciated source of genome instability [1–3], but to what extent this happens in vivo remains unknown. Here we consider an in vivo system where the adult stem cells of planarian flatworms are required to migrate to a distal wound site [4]. We observe a relationship between adult stem cell migration and ongoing DNA damage and repair during tissue regeneration. Migrating planarian stem cells undergo changes in nuclear shape and increased levels of DNA damage. Increased DNA damage levels resolve once stem cells reach the wound site and stop migrating. Stem cells in which DNA damage is induced prior to wounding take longer to initiate migration suggesting migration activity is sensitive to DNA damage. Migrating stem cells populations are more sensitive to further DNA damage than stationary stem cells, providing evidence that levels of migration-coupled-DNA-damage (MCDD) are significant. RNAi mediated knockdown of DNA repair pathway components blocks normal stem cell migration, confirming that DNA repair pathways are required to allow successful migration to a distal wound site. Together these lines of evidence demonstrate that migration leans to DNA damage in vivo and requires DNA repair mechanisms. Our findings reveal that migration of stem cells represents an unappreciated source of damage, that could be a significant source of mutations in animals during development or during long term tissue homeostasis.