Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Nov 2:11:39.
doi: 10.1186/1475-2867-11-39.

Translesion DNA synthesis in the context of cancer research

Philip A Knobel  1 , Thomas M Marti
Affiliations

Translesion DNA synthesis in the context of cancer research

Philip A Knobel et al. Cancer Cell Int. .

Abstract

During cell division, replication of the genomic DNA is performed by high-fidelity DNA polymerases but these error-free enzymes can not synthesize across damaged DNA. Specialized DNA polymerases, so called DNA translesion synthesis polymerases (TLS polymerases), can replicate damaged DNA thereby avoiding replication fork breakdown and subsequent chromosomal instability.We focus on the involvement of mammalian TLS polymerases in DNA damage tolerance mechanisms. In detail, we review the discovery of TLS polymerases and describe the molecular features of all the mammalian TLS polymerases identified so far. We give a short overview of the mechanisms that regulate the selectivity and activity of TLS polymerases. In addition, we summarize the current knowledge how different types of DNA damage, relevant either for the induction or treatment of cancer, are bypassed by TLS polymerases. Finally, we elucidate the relevance of TLS polymerases in the context of cancer therapy.

PubMed Disclaimer

Figures

Figure 1
Figure 1
DNA damage induced by spontaneous decay or endogenous and environmental sources can either be repaired or tolerated (Adapted from [245]). See text for details.
Figure 2
Figure 2
Overview of TLS polymerases (Adapted from [246]). See text for details.
Figure 3
Figure 3
One- polymerase error-free bypass of a UV-induced TT-CPD carried out by TLS Pol η (adapted from [247]). See text for details.
Figure 4
Figure 4
Two-polymerase mechanisms for bypassing BaP-G (top) or cisplatin (cisPt) (bottom) DNA adducts. The insertion step is performed by one or a combination of several TLS polymerases incorporating nucleotides in an error-free or error-prone manner opposite the adduct whereas the extension step is mainly carried out by TLS Pol ζ (adapted from [247]). See text for details.
Figure 5
Figure 5
Trade-off between the accumulation of mutations due to DNA lesion bypass by TLS and the accumulation of genomic instability in the absence of TLS.
See this image and copyright information in PMC

References

    1. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W. et al.Initial sequencing and analysis of the human genome. Nature. 2001;409(6822):860–921. - PubMed
    1. Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA. et al.The sequence of the human genome. Science. 2001;291(5507):1304–1351. - PubMed
    1. Lindahl T, Barnes DE. Repair of endogenous DNA damage. Cold Spring Harb Symp Quant Biol. 2000;65:127–133. - PubMed
    1. Barnes DE, Lindahl T. Repair and genetic consequences of endogenous DNA base damage in mammalian cells. Annu Rev Genet. 2004;38:445–476. - PubMed
    1. Hecht SS. Tobacco smoke carcinogens and lung cancer. J Natl Cancer Inst. 1999;91(14):1194–1210. - PubMed

LinkOut - more resources