Phosphotriester adducts (PTEs): DNA's overlooked lesion.

Mutagenesis
George D D JonesPeter B Farmer

Abstract

In addition to reacting with DNA base moieties, many chemical genotoxins also react with the oxygen atoms of the internucleotidic phosphodiester linkages to form phosphotriester adducts (PTEs). In view of their stability under physiological conditions, it has been suggested that PTEs may be useful biomarkers for measuring cumulative genotoxin exposure. The methodology for their determination is varied and still not completely developed but includes determination of hydrolysis products and (32)P-postlabelling approaches. More recently, transalkylation and direct mass spectrometry techniques have been devised, which give extra chemical information on the structures of the PTEs. The proportion of DNA damage formed as PTEs is much greater with SN1 compared to SN2 alkylating agents, and it has been shown in DNA that the formation of PTEs is partially sequence dependent. PTEs have been considered to be refractory to repair in mammalian cells but repair mechanisms have been found in prokaryotic cells, e.g. PTEs in Escherichia coli are repaired by O(6)-methylguanine-DNA methyltransferase (O(6)-MGT or Ada protein). However, studies on in vivo persistence of PTEs in mammalian systems have not ruled out the possibility of a contribution f...Continue Reading

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Citations

Apr 14, 2012·The Journal of Biological Chemistry·Avvaru N SuhasiniRobert M Brosh
Nov 10, 2011·Environmental and Molecular Mutagenesis·Leslie RecioKristine L Witt
Jul 15, 2015·DNA Repair·Irfan KhanRobert M Brosh
Nov 7, 2014·Frontiers in Genetics·Robert M Brosh, Sharon B Cantor
Sep 17, 2013·ACS Synthetic Biology·Felix MoserChristopher A Voigt
Jun 19, 2019·Archives of Toxicology·S ShangulaA C Povey
Jan 10, 2020·Chemical Research in Toxicology·Jiabin Wu, Yinsheng Wang
Oct 7, 2021·Environmental Science and Pollution Research International·Smita KumariRashmi K Ambasta

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