Extended Data Fig. 9: CSB is required for the repair of DPCs at transcriptionally active loci.
From: Transcription-coupled repair of DNA–protein cross-links depends on CSA and CSB
(a) DPC-seq coverage per gene, with or without 6 h recovery after treatment, in genes grouped by transcriptional activity, as determined by RNAPII ChIP-seq (GEO: GSE141798)59, statistics via two-sided paired Wilcoxon test ** p < 0.01 *** p < 0.001; p-values are 0.1458, 0.008734, <2.2 × 10−16 and <2.2 × 10−16 for comparisons in low, mid-low, mid-high and high transcriptional activity gene sets, respectively. (b) DPC-seq coverage per gene in WT RPE1 cells vs CSB−/− cells immediately (0 h) after formaldehyde treatment, blue genes show significantly enriched DPC coverage in CSB−/− cells. (c) Percentage of different gene types in genes that are dependent on CSB for DPC repair or where repair is not significantly changing based on CSB status. (d) RNAPII occupancy of genes that are dependent or independent on CSB for DPC repair, statistics via two-sided unpaired Wilcoxon test *** p < 0.001; p < 2.2 × 10−16. (e) Same as (d) but for DNA accessibility; p < 2.2 × 10−16. (f) Same as (d) but for gene length; p = 7.457 × 10−11. (g) Box-plot of DPC-seq coverage per gene in WT and CSB−/− cells with 1 h 1.75 mM formaldehyde treatment with or without 6 h recovery split into quartiles of transcriptional activity, statistics via two-sided Dunn test (paired) * p < 0.05 *** p < 0.001; p-values are 0.2265 and 0.05998 (low transcriptional activity, 0 h and 6 h respectively), 0.0007959 and 0.03377 (mid-low transcriptional activity, 0 h and 6 h respectively), 0.5608 and 2.466 × 10−10 (mid-high transcriptional activity, 0 h and 6 h respectively), 0.2227 and <2.2 × 10−16 (high transcriptional activity, 0 h and 6 h respectively). (a, d-g) Box-plot shows upper (Q3) and lower (Q1) quartile boundaries and line at the median. Lower whisker (minimum) = Q1 – 1.5 x interquartile range (IQR), upper whisker (maximum) = Q3 + 1.5 x IQR. For all DPC-seq analyses, n = 3 biological replicates. Source numerical data are available in source data.
