Mechanism of Error-Free DNA Replication Past Lucidin-Derived DNA Damage by Human DNA Polymerase κ.

DNA damage impinges on genetic information flow and has significant implications in human disease and aging. Lucidin-3-O-primeveroside (LuP) is an anthraquinone derivative present in madder root, which has been used as a coloring agent and food additive. LuP can be metabolically converted to genotoxic compound lucidin, which subsequently forms lucidin-specific N2-2'-deoxyguanosine (N2-dG) and N6-2'-deoxyadenosine (N6-dA) DNA adducts. Lucidin is mutagenic and carcinogenic in rodents but has low carcinogenic risks in humans. To understand the molecular mechanism of low carcinogenicity of lucidin in humans, we performed DNA replication assays using site-specifically modified oligodeoxynucleotides containing a structural analogue (LdG) of lucidin-N2-dG DNA adduct and determined the crystal structures of DNA polymerase (pol) κ in complex with LdG-bearing DNA and an incoming nucleotide. We examined four human pols (pol η, pol ι, pol κ, and Rev1) in their efficiency and accuracy during DNA replication with LdG; these pols are key players in translesion DNA synthesis. Our results demonstrate that pol κ efficiently and accurately replicates past the LdG adduct, whereas DNA replication by pol η, pol ι is compromised to different extents. Rev1 retains its ability to incorporate dCTP opposite the lesion albeit with decreased efficiency. Two ternary crystal structures of pol κ illustrate that the LdG adduct is accommodated by pol κ at the enzyme active site during insertion and postlesion-extension steps. The unique open active site of pol κ allows the adducted DNA to adopt a standard B-form for accurate DNA replication. Collectively, these biochemical and structural data provide mechanistic insights into the low carcinogenic risk of lucidin in humans.

[Photoelectrocatalytic degradation of bisphenol A in water by Fe doped-TiO2 nanotube arrays under simulated solar light irradiation].

Seeking an efficient treatment method for bisphenol A ( BPA), a representative endocrine disrupting compound, is important for environmental remediation and human health. Herein, the degradation of BPA by means of photoelectrocatalysis was investigated. Fe doped-TiO2 nanotube arrays ( Fe/TNA ) served as the photoanode, and a xenon lamp simulated the solar light source. First, undoped TiO2 nanotube arrays (TNA) and a series of Fe/TNA were characterized by field emission scanning electron microscopy, X-ray diffraction and UV-Vis diffuse reflectance spectroscopy. The UV-Vis absorption spectra of Fe/TNA showed a red-shift and an enhancement of the absorption in the visible-light region compared to TNA. Then, experimental conditions including Fe doping content, current intensity and aeration rate were varied to demonstrate their effects on the elimination of BPA. It was observed that the degradation of BPA could be fitted to the quasi-first-order equation. Under the following conditions: Fe/TNA prepared by 0.9 mol x L(-1) Fe(NO3)3 solution dip-coating as photoanode, titanium foil as cathode, current intensity of 1.15 mA x cm(-2) and initial BPA concentration of 10 mg x L(-1), 72.3% BPA was decomposed during 4 h reaction, with a rate constant of 5.32 x 10(-3) min(-1). Aeration enhanced the removal rate of BPA to 82.7% and 94.1% with an aerating rate of 1.0 L x min(-1) using titanium foil as cathode and an aerating rate of 0.2 L x min(-1) using carbon cloth as cathode, respectively, and the corresponding rate constants were 7.20 x 10(-3) min(-1) and 11.6 x 10(-3) min(-1), respectively.