Journal
GENES & DEVELOPMENT
Volume 24, Issue 2, Pages 123-128Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.1872810
Keywords
Replicative lesion bypass; DNA replication; (6-4) photoproducts; UV damage; DNA repair
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Funding
- National Institute of Environmental Health Sciences (NIEHS) [ES012411, P30-ES06676]
- NCI [T32CA117834]
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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.
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