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. 2016 Sep 19;3(6):e1225547.
doi: 10.1080/23723556.2016.1225547. eCollection 2016.

Cancer cells activate damage-tolerant and error-prone DNA synthesis

Elizabeth Mutter-Rottmayer  1 , Yanzhe Gao  2 , Cyrus Vaziri  2
Affiliations

Cancer cells activate damage-tolerant and error-prone DNA synthesis

Elizabeth Mutter-Rottmayer et al. Mol Cell Oncol. .

Abstract

Trans-lesion synthesis (TLS) is a DNA damage-tolerant and error-prone mode of DNA replication. Recent work shows that many cancer cells coopt an aberrantly expressed germ cell protein, melanoma antigen-A4 (MAGE-A4), to activate TLS. MAGE-A4-induced "pathological TLS" provides a potential mechanism through which neoplastic cells can tolerate intrinsic and therapeutic genotoxicity while acquiring mutability.

Keywords: Cancer-testes antigens (CTA); DNA damage; RAD18; genome maintenance; melanoma antigen-A4 (MAGE-A4); mutagenesis; trans-lesion synthesis (TLS).

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Figures

Figure 1.
Figure 1.
Potential roles of MAGE-A4–driven trans-lesion synthesis in tumorigenesis. Melanoma antigen-A4 (MAGE-A4)-induced TLS provides a mechanism by which neoplastic cells can tolerate carcinogenic exposures, oncogenic DNA replication stress, and therapy-induced DNA damage while promoting mutagenesis. The MAGE-A4–RAD18 signaling axis may provide opportunities for therapies that are highly specific for cancer cells.
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References

    1. Prakash S, Johnson RE, Prakash L. Eukaryotic translesion synthesis DNA polymerases: specificity of structure and function. Annu Rev Biochem 2005; 74:317-53; PMID:15952890; http://dx.doi.org/ 10.1146/annurev.biochem.74.082803.133250 - DOI - PubMed
    1. Masutani C, Kusumoto R, Yamada A, Dohmae N, Yokoi M, Yuasa M, Araki M, Iwai S, Takio K, Hanaoka F. The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta. Nature 1999; 399:700-4; PMID:10385124; http://dx.doi.org/ 10.1038/21447 - DOI - PubMed
    1. Gao Y, Mutter-Rottmayer E, Greenwalt AM, Goldfarb D, Yan F, Yang Y, Martinez-Chacin RC, Pearce KH, Tateishi S, Major MB, et al. A neomorphic cancer cell-specific role of MAGE-A4 in trans-lesion synthesis. Nature communications 2016; 7:12105; PMID:27377895; http://dx.doi.org/ 10.1038/ncomms12105 - DOI - PMC - PubMed
    1. Hedglin M, Benkovic SJ. Regulation of Rad6/Rad18 activity during DNA damage tolerance. Annual review of biophysics 2015; 44:207-28; PMID:26098514; http://dx.doi.org/ 10.1146/annurev-biophys-060414-033841 - DOI - PMC - PubMed
    1. Simpson AJ, Caballero OL, Jungbluth A, Chen YT, Old LJ. Cancer/testis antigens, gametogenesis and cancer. Nat Rev Cancer 2005; 5:615-25; PMID:16034368; http://dx.doi.org/ 10.1038/nrc1669 - DOI - PubMed

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