Fig. 4: Competition between Dam-mediated DNA methylation and strand cleavage by MutH causes MMR failures.

Repair efficiency is modulated by deletion of mutH (mutH, blue), overexpression of Dam (WT PLtetO1-dam, violet), overexpression of MutH (WT pMutH, yellow), and deletion of dam (dam, cyan). These conditions are compared to the wild-type (WT, red). a Rate of long-lived foci. (inset: zoom-in of the results for WT, WT pMutH, and dam). The bars represent the average of individual experiments (dots, 3 experiments per condition except for dam for which there are 4 experiments). b The distribution of YFP-MutL foci lifetimes is shown for one representative experiment of each condition shown in panel (a). All replicates are presented in Supplementary Fig. 7. c Competition between Dam and MutH determines the fate of replication errors detected by MMR. After MutS (red rectangle) and MutL (yellow star) binding, if MutH (green triangle) binds to the unmethylated GATC site before Dam (purple circle), the error is repaired, leading to a short-lived YFP-MutL focus (left side, yellow-shaded areas of the schematic). On the contrary, if Dam binds earlier than MutH to the unmethylated GATC site, MutH cannot initiate repair, leading to a long-lived YFP-MutL focus representative of a nascent mutation (right side, pink-shaded areas of the schematic). Source data are provided as a Source Data file.