Error-free replicative bypass of (6–4) photoproducts by DNA polymerase ζ in mouse and human cells
- Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, Galveston, Texas 77555, USA
Abstract
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 η and Pol ι provide alternate pathways for mutagenic TLS, surprisingly, Pol ζ 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.
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Footnotes
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↵1 Corresponding author.
E-MAIL s.prakash{at}utmb.edu; FAX (409) 747-8610.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1872810.
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Supplemental material is available at http://www.genesdev.org.
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- Received October 11, 2009.
- Accepted November 20, 2009.
- Copyright © 2010 by Cold Spring Harbor Laboratory Press