Martin–Pardillos A et al. – This study investigated how stem and proliferating cells manage accumulating endogenous deoxyribonucleic acid (DNA) lesions, and their final effect on physiology of cells and tissues. The results of the study revealed that hematopoietic system protects its genomic and functional integrity by depending to a great extent on the combined activities of repair and replication of helix–distorting oxidative nucleotide lesions by global–genome nucleotide excision repair (ggNER) and Rev1 (core factor in DNA synthesis)–dependent translesion synthesis (TLS), respectively. Thus, a mechanistic understanding of accumulation of mutations in the hematopoietic system upon aging can be provided by the error–prone nature of TLS.