Metabolism Lipid Metabolism

Arajo, Ulrike Fiedler, Wim Vermeulen, Frederic Coin, JeanMarc Egly, Jan H.Biol. Chem. doi. jbc. Access the most updated version of this article at http:www.jbc.orgcontent When a correction for this article is posted Click here to choose from all of JBCs email alerts This article cites references, of which can be accessed free at http:www.jbc.orgcontent.full.htmlreflist Downloadedfromhttp: www.jbc.orgbyguestonSeptember, We found that a phosphorothioate and a methylphosphonate were excised with low efficiency.Considering the relative abundance of undamaged DNA in comparison to damaged DNA in the course of the life of an organism, we conclude that, in general, excision from and resynthesis of undamaged DNA may exceed the excision and resynthesis caused by DNA damage.As resynthesis is invariably associated with mutations, we propose that gratuitous repair may be an important source of spontaneous mutations.Nucleotide excision repair is a general repair system that removes damaged bases from DNA by dual incisions of the damaged strand at some distance from the lesion, releasing the damaged base in the form of mers in prokaryotes and mers in eukaryotes. It is the major repair system for bulky base adducts, but it also acts on nonbulky lesions such as oxidized or methylated bases and, as such, functions as a backup system for DNA glycosylases, which have restricted substrate ranges. With regard to substrate range, its limits remain to be defined.The excision nuclease, which originally was thought to be specific for bulky lesions, was later found to excise nonbulky adducts such as methylated bases but, apparently, failed to excise nucleotides with backbone modifications such as the C pivaloyl adduct we decided to reexamine the question of recognition of backbone modifications.The costs of publication of this article were defrayed in part by the payment of page charges.This article must therefore be hereby marked advertisement in accordance with U.This, in turn, led us to take a closer look at the effect of the enzyme system on undamaged DNA.This gratuitous excision and the inevitable repair synthesis that must follow could be potential sources of spontaneous mutations.Our data suggest that even in nondividing cells in which there is no DNA replication, there can be significant DNA turnover due to gratuitous excision and resynthesis and that this gratuitous repair may cause mutations in such cells, even when they are protected from all extrinsic and intrinsic DNA damaging agents.The methylphosphonatecontaining mer, the phosphorothioatecontaining mer, and the hydroxyguaninecontaining. The sequence of the centrally located mers was GAAGCTACGAGC with the phosphorothioate or methylphosphonate modifications between C and T.A, the phosphorothioate adducted thymidines introduce minor alterations into the sugarphosphate backbone and are shown next to undamaged are damaged bases generated by reactive oxygen species; these lesions cause minor helical distortions.The lower panel illustrates three bulky, helixdistorting lesions introduced either by ultraviolet radiation, such as cyclobutane thymine dimer diadduct. Following the reaction, the DNA was extracted with phenol:chloroform, and the deproteinized DNA was precipitated with ethanol, resuspended in formamidedye mixture, and resolved in polyacrylamide gels containing M urea to separate excision products from substrate DNA.The extent of excision for each reaction was determined from the percentage of signal migrating as; mers relative to the signal for fulllength DNA.

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