Error-free replicative bypass of (6-4) photoproducts by DNA polymerase zeta in mouse and human cells.
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.
Yoon
Jung-Hoon
JH
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, Galveston, Texas 77555, USA.
Prakash
Louise
L
Prakash
Satya
S
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004249:DNA Damage / Q000528:radiation effects; D004260:DNA Repair; D004261:DNA Replication / Q000235:genetics*; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D006801:Humans; D051379:Mice; D011740:Pyrimidine Dimers / Q000235:genetics*; D014466:Ultraviolet Rays
D011740:Pyrimidine Dimers; C058406:pyrimidine-pyrimidone dimer; D004259:DNA-Directed DNA Polymerase