Error-free replicative bypass of (6-4) photoproducts by DNA polymerase zeta in mouse and human cells

Genes Dev. 2010 Jan 15;24(2):123-8. doi: 10.1101/gad.1872810.


The ultraviolet (UV)-induced (6-4) pyrimidine-pyrimidone photoproduct [(6-4) PP] confers a large structural distortion in DNA. Here we examine in human cells the roles of translesion synthesis (TLS) DNA polymerases (Pols) in promoting replication through a (6-4) TT photoproduct carried on a duplex plasmid where bidirectional replication initiates from an origin of replication. We show that TLS contributes to a large fraction of lesion bypass and that it is mostly error-free. We find that, whereas Pol eta and Pol iota provide alternate pathways for mutagenic TLS, surprisingly, Pol zeta functions independently of these Pols and in a predominantly error-free manner. We verify and extend these observations in mouse cells and conclude that, in human cells, TLS during replication can be markedly error-free even opposite a highly distorting DNA lesion.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line
  • Cells, Cultured
  • DNA Damage* / radiation effects
  • DNA Repair
  • DNA Replication / genetics*
  • DNA-Directed DNA Polymerase / metabolism*
  • Humans
  • Mice
  • Pyrimidine Dimers / genetics*
  • Ultraviolet Rays


  • Pyrimidine Dimers
  • pyrimidine-pyrimidone dimer
  • DNA-Directed DNA Polymerase