Base Excision DNA Repair Deficient Cells: From Disease Models to Genotoxicity Sensors

Author(s): Daria V. Kim, Alena V. Makarova, Regina R. Miftakhova, Dmitry O. Zharkov*.

Journal Name: Current Pharmaceutical Design

Volume 25 , Issue 3 , 2019


Base excision DNA repair (BER) is a vitally important pathway that protects the cell genome from many kinds of DNA damage, including oxidation, deamination, and hydrolysis. It involves several tightly coordinated steps, starting from damaged base excision and followed by nicking one DNA strand, incorporating an undamaged nucleotide, and DNA ligation. Deficiencies in BER are often embryonic lethal or cause morbid diseases such as cancer, neurodegeneration, or severe immune pathologies. Starting from the early 1980s, when the first mammalian cell lines lacking BER were produced by spontaneous mutagenesis, such lines have become a treasure trove of valuable information about the mechanisms of BER, often revealing unexpected connections with other cellular processes, such as antibody maturation or epigenetic demethylation. In addition, these cell lines have found an increasing use in genotoxicity testing, where they provide increased sensitivity and representativity to cell-based assay panels. In this review, we outline current knowledge about BER-deficient cell lines and their use.

Keywords: DNA repair, base excision repair, knockout cell lines, genotoxicity assays, mutagenesis, epigenetic demethylation.

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Article Details

Year: 2019
Page: [298 - 312]
Pages: 15
DOI: 10.2174/1381612825666190319112930
Price: $65

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