Modifications of DNA clamps and their role in DNA damage management

We show that proliferating cell nuclear antigen (PCNA) modification plays an important role in the efficient regulation of mammalian translesion DNA synthesis (TLS), but, as opposed to lower eukaryotes such as yeast, TLS polymerases can also be activated without ubiquitinated PCNA (PCNA-Ub). Future experiments should investigate the molecular nature of PCNA-Ub-independent TLS activation. Furthermore, DNA damage tolerance (DDT) by TLS is clinically relevant, as shown by deregulation in certain cancers and a suspected role in chemoresistance. Moreover, inhibition of DDT provides an attractive therapeutic drug target for chemosensitization.