Revl Is a dCMP Transferase

Although the molecular defect of XPV is very different from that of the other XP patients (XPA, XPB, XPC, XPD, XPE, XPF, and XPG), who are deficient in nucleotide excision repair, the clinical manifestations of the diseases are quite similar. This is not surprising because the defect in either Polq or nucleotide excision repair results in a common problem genomic overload of TT dimers and perhaps other CPDs for error-prone translesion synthesis by other bypass polymerases during replication. The result is predictable elevated cytotoxicity and mutagenesis induced by the UV component of the sunlight, which constitute the cellular bases of XP diseases. 

7c DNA Polymerase k. The hallmark of PoIk is efficient error-free bypass of (-)-trans-anti-BPV V-N2-dG adducts discovered by Zhigang Wang and colleagues. Polic also bypasses the (+)-trans-anti-HV )E-jV-dG adduct with the correct C 

Poll is capable of both error-free and error-prone translesion syntheses in vitro. In response to 8-oxoguanine in DNA, human Poll predominantly incorporates C opposite the lesion. Fluman Poll is able to incorporate the correct C opposite the AAF-adducted guanine. Flowever, further DNA synthesis is blocked by the lesion. Fluman Poll incorporates one nucleotide opposite a template AP site more efficiently than opposite a template T, with the incorporation specificity of G T A C. After incorporating one nucleotide opposite the AP site, further DNA synthesis is aborted. 

Surprisingly, human Poll prefers A incorporation opposite the 3 T of a template TT (6-4) photoproduct, in contrast to the much preferred G incorporation opposite the undamaged template T. Nucleotide incorporation opposite the 5 T of the TT (6-4) photoproduct, however, is largely blocked by the lesion. Opposite a template TT dimer, human Poll has a very limited activity, preferentially incorporating a T opposite the 3 T of the lesion. This activity, albeit very inefficient, may contribute to TT dimer-induced mutagenesis in XPV cells that lack Polr.  

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