Infection of cells with pks positive E. coli activates the classical DNA interstrand cross-links repair pathway resulting in: (i) monoubiquitination and recruitment of FANCD2 at stalled replication forks; (ii) ATR-dependent phosphorylation of CHK1 and RPA; (iii) activation of the DSB repair pathway, including phosphorylation of ATM, H2AX, and CHK2, and 53BP1 foci formation in response to replication stress-mediated DSBs; (iv) induction of cell cycle arrest and senescence [35,41]. Here, ARAF is linked to infection.