Extended Data Fig. 1: ERCC6/CSB mediates cellular tolerance of DPCs.

(a) Venn diagram and STRING analysis at medium confidence (cutoff = 0.400) showing common hits (resistance or sensitivity) from formaldehyde and 5-aza-dC CRISPRi screens in K562 cells. (b) Schematic depiction of formaldehyde detoxification by ADH5 and ESD. (c) Schematic showing 5-aza-dC uptake into cells and subsequent phosphorylation events, mediated by DCK and CMPK1, that are necessary for 5-aza-dC incorporation into nascent DNA. (d-f) Clonogenic survival assays in WT or CSB^−/− TET3G cells in the absence of doxycycline, treated with formaldehyde (d), 5-aza-dC (e) or Illudin S (f); data are presented as mean ± SEM, n = 3 replicates. (g-h) Clonogenic survival assays in MRC5 lung fibroblasts and CSB-deficient fibroblasts (CS1AN) treated with formaldehyde (g) or 5-aza-dC (h); data are presented as mean ± SEM, n = 3 replicates. (i-k) Alamar blue viability assays in WT, CSB^−/−, XPC^−/− or CSB^−/−/XPC^−/− RPE1 cells treated with formaldehyde (i), 5-aza-dC (j) or Illudin S (k); data are presented as mean ± SD, n = 3 replicates. (l) Colony formation assay in the cell lines from (i-k) treated with UVC at the indicated doses. (m) Representative oligonucleotide excision assay in WT and XPC^−/− RPE1 cells treated with formaldehyde (FA) or UVC and released from treatment as indicated. A 50nt oligonucleotide was spiked in as an internal control. (n) Quantification of (m); data are presented as mean ± SD, n = 3 replicates. Source numerical data are available in source data.