Characterization of human translesion DNA synthesis across a UV-induced DNA lesion.

Translesion DNA synthesis (TLS) during S-phase uses specialized TLS DNA polymerases to replicate a DNA lesion, allowing stringent DNA synthesis to resume beyond the offending damage. Human TLS involves the conjugation of ubiquitin to PCNA clamps encircling damaged DNA and the role of this post-translational modification is under scrutiny. A widely accepted model purports that ubiquitinated PCNA recruits TLS polymerases such as pol eta to sites of DNA damage where they may also displace a blocked replicative polymerase. We provide extensive quantitative evidence that the binding of pol eta to PCNA and the ensuing TLS are both independent of PCNA ubiquitination. Rather, the unique properties of pols eta and delta are attuned to promote an efficient and passive exchange of polymerases during TLS on the lagging strand.