Kinetic Investigation of Translesion Synthesis across a 3-Nitrobenzanthrone-Derived DNA Lesion Catalyzed by Human DNA Polymerase Kappa.

3-Nitrobenzanthrone (3-NBA) is a byproduct of diesel exhaust and is highly present in industrial and populated areas. Inhalation of 3-NBA results in formation of -(2'-deoxyguanosin-8-yl)-3-aminobenzanthrone (dG), a bulky DNA lesion that is of concern due to its mutagenic and carcinogenic potential. If dG is not bypassed during genomic replication, the lesion can stall cellular DNA replication machinery, leading to senescence or apoptosis.

Significant impact of divalent metal ions on the fidelity, sugar selectivity, and drug incorporation efficiency of human PrimPol.

Human PrimPol is a recently discovered bifunctional enzyme that displays DNA template-directed primase and polymerase activities. PrimPol has been implicated in nuclear and mitochondrial DNA replication fork progression and restart as well as DNA lesion bypass. Published evidence suggests that PrimPol is a Mn-dependent enzyme as it shows significantly improved primase and polymerase activities when binding Mn, rather than Mg, as a divalent metal ion cofactor.