Short Title: 53bp1 supports p53-family transcriptional program

Here, we present Automated Multimodal Multiplexed Microscopy for Image CytOmetry (A.M3.I.CO), a correlative imaging platform that combines multiscale resolution, from millimeters to nanometers, with automated workflows for high-throughput phenotypic profiling and targeted single-molecule analysis in-situ.

Applying A.M3.I.CO, we observed that 53BP1 is recruited at transcribed p53-target genes independently of the activating stimuli, with evidence for a putative complex formation involving 53BP1, p53, and the basal transcription machinery, as also demonstrated by in-vivo observations in tumor models. This localization extends to p63- and p73-targeted transcription sites, suggesting a broader role for 53BP1 in participating to p53 family–dependent transcription.