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Stepwise Translocation of Dpo4 Polymerase during Error-Free Bypass of an oxoG Lesion
Stepwise conformational transitions accompanying nucleoside triphosphate binding and covalent nucleobase incorporation during a full replication cycle of Dpo4-catalyzed bypass of the oxoG lesion are distinct from the translocation events in replicative polymerases. Expand
Error-free and error-prone lesion bypass by human DNA polymerase κ in vitro
It is shown that human Polκ is a novel lesion bypass polymerase in vitro and its response to damaged DNA templates suggests that Polκ plays an important role in both error-free and errorproneLesion bypass in humans. Expand
Quantitative Analysis of Translesion DNA Synthesis across a Benzo[a]pyrene-Guanine Adduct in Mammalian Cells
- S. Avkin, M. Goldsmith, S. Velasco-Miguel, N. Geacintov, E. Friedberg, Z. Livneh
- Biology, Medicine
- Journal of Biological Chemistry
- 17 December 2004
Translesion DNA synthesis (TLS) across a benzo[a]pyrene-guanine (BP-G) adduct, a major mutagenic DNA lesion generated by tobacco smoke, is studied to indicate that BP-G is bypassed in mammalian cells with relatively high efficiency and that polκ bypasses BP- G in vivo with higher efficiency and higher accuracy than other DNA polymerases. Expand
Error-prone lesion bypass by human DNA polymerase eta.
Results show that human Pol(eta) is capable of error-prone translesion DNA syntheses in vitro and suggest that Pol (eta) may bypass certain lesions with a mutagenic consequence in humans. Expand
DNA polymerase ζ cooperates with polymerases κ and ι in translesion DNA synthesis across pyrimidine photodimers in cells from XPV patients
- O. Ziv, N. Geacintov, S. Nakajima, A. Yasui, Z. Livneh
- Biology, Medicine
- Proceedings of the National Academy of Sciences
- 14 July 2009
It is shown that DNA polymerase ζ cooperates with DNA polymerases κ and ι to carry out error-prone TLS across a TT CPD, which presents an extreme example of benefit-risk balance in the activity of TLS polymerases, which provide protection against UV cytotoxicity at the cost of increased mutagenic load. Expand
Two‐polymerase mechanisms dictate error‐free and error‐prone translesion DNA synthesis in mammals
Results highlight the central role of polζ in both error‐prone and error‐free TLS in mammalian cells, and show that bypass of a single lesion may involve at least three different DNA polymerases, operating in different two‐polymerase combinations. Expand
p53 and p21 regulate error-prone DNA repair to yield a lower mutation load.
It is found that in mammalian cells TLS is controlled by the tumor suppressor p53, and by the cell cycle inhibitor p21 via its PCNA-interacting domain, to maintain a low mutagenic load at the price of reduced repair efficiency. Expand
Unrepaired fjord region polycyclic aromatic hydrocarbon-DNA adducts in ras codon 61 mutational hot spots.
Findings indicate that the exceptional tumorigenic potency of B[c]Ph or related fjord region diol-epoxides may be attributed, at least in part, to slow repair of the stable base adducts deriving from the reaction of these compounds with DNA. Expand
The Chemical Biology of DNA Damage
Preface. List of Contributors. PART ONE Chemistry and Biology of DNA Lesions. 1 Introduction and Perspectives on the Chemistry and Biology of DNA Damage (Nicolas E. Geacintov and Susan Broyde). 1.1… Expand