Translesion DNA synthesis in eukaryotes: A one- or two-polymerase affair

Cellular DNA is continually damaged by a plethora of extrinsic and intrinsic sources, including UV light from the sun and reactive oxygen species resulting from aerobic respiration. Although cells possess a variety of repair processes to remove DNA lesions, lesions that escape repair can block the replicational machinery, and there has been little understanding of the mechanisms by which eukaryotic cells overcome such blocks and promote the continuity of the newly replicated DNA strand. The past three years, however, have witnessed phenomenal progress in this area of research, and here we highlight the important findings and major conclusions that have emerged regarding translesion DNA synthesis (TLS) in eukaryotes.