|| Checking for direct PDF access through Ovid
DNA interstrand crosslinks (ICLs) are induced by a number of bifunctional antitumor drugs such as cisplatin, mitomycin C, or the nitrogen mustards as well as endogenous agents formed by lipid peroxidation. The repair of ICLs requires the coordinated interplay of a number of genome maintenance pathways, leading to the removal of ICLs through at least two distinct mechanisms. The major pathway of ICL repair is dependent on replication, homologous recombination, and the Fanconi anemia (FA) pathway, whereas a minor, G0/G1-specific and recombination-independent pathway depends on nucleotide excision repair. A central step in both pathways in vertebrates is translesion synthesis (TLS) and mutants in the TLS polymerases Rev1 and Pol ζ are exquisitely sensitive to crosslinking agents. Here, we review the involvement of Rev1 and Pol ζ as well as additional TLS polymerases, in particular, Pol η, Pol κ, Pol ι, and Pol ν, in ICL repair. Biochemical studies suggest that multiple TLS polymerases have the ability to bypass ICLs and that the extent of bypass depends upon the structure as well as the extent of endo- or exonucleolytic processing of the ICL. As has been observed for lesions that affect only one strand of DNA, TLS polymerases are recruited by ubiquitinated proliferating nuclear antigen (PCNA) to repair ICLs in the G0/G1 pathway. By contrast, this data suggest that a different mechanism involving the FA pathway is operative in coordinating TLS in the context of replication-dependent ICL repair. Environ. Mol. Mutagen. 51:552-566, 2010.