Tissue-specific mutagenesis from endogenous guanine damage is suppressed by PolK and DNA repair

We report here LC-MS data using targeted adductomics and biochemical analyses to identify endogenous N2-dG lesions requiring Polk-mediated bypass, and untargeted adductomics to reveal new guanine lesions that engage NER. These findings uncover the nature of endogenous DNA damage and the coordinated roles of repair and tolerance pathways that limit mutagenesis in tissues.
, Quantitative Parallel Reaction Monitoring (PRM) of Endogenous Adducts 
Samples from wild type, Xpa -/-, and Xpc -/- liver and kidney DNA were reconstituted in 20 μL of H2O for LC-MS2 analysis targeting known endogenous DNA adducts. The analysis was done using an Orbitrap Exploris 480 instrument (ThermoFisher) coupled to a Vanquish™ Neo UHPLC system (Thermo Fisher) using positive nanoelectrospray ionization (NSI) with a source temperature of 300°C and a spray voltage of 1900V. The reversed-phase chromatographic separation was performed using a nanoflow column (50 cm x 75 μm, CoAnn Technologies, Richland, WA) self-packed with Luna C18 (5 μm,100 Å, Phenomenex) stationary phase. The mobile phases consisted of 5 mM NH4OAc (A) and 95 % CH3CN in H2O (B), and the injection volume was 4 μL. The gradient started with an increase from 1 % to 5 % B over 5 min at a flow rate of 0.3 μL/min, followed by an increase to 22 % B over 30 min. The gradient was then increased to 95 % B over 1 min, and t..., # Data from: Tissue-specific mutagenesis from endogenous guanine damage is suppressed by PolK and DNA repair

Dataset DOI: [10.5061/dryad.r4xgxd2sp](https://doi.org/10.5061/dryad.r4xgxd2sp)

## Description of the data and file structure

Targeted adductomics data was collected to identify endogenous *N^2^*-dG lesions (guanine DNA adducts) which require Polk-meditated bypass. Untargeted adductomics was used to reveal new guanine lesions that engage NER. These findings uncover the nature of endogenous DNA damage and the coordinated roles of repair and tolerance pathways that limit mutagenesis in tissues.

The DNA adductomic screening for both the known endogenous and unknown putative DNA adducts was performed using the data in the Untargeted_LC-MS2MS3_Screening.zip folder. The file names are self-explanatory. The letters \"WT\" in the file name indicate \"Wild-type\" and these files served as negative controls and \"Range\" indicate different mass ranges which was done to breaking up the analys...,