Fig. 2: EP300-mutated cells have aberrant replication dynamics associated with increased origin firing.

A Locus map of a 375 kb region in the CFS-FRA6E obtained by PmeI digestion. The region includes the fragility core of CFS-FRA6E (pink line – 162 kb). The FISH probes that identify the segment are labeled in blue. Top: Locus map of the PmeI-digested FRA6E segment. Bottom: Aligned photomicrograph images of labeled DNA molecules from the DNA Replication program at CFS-FRA6E in (B) J-ATLL EP300WT (J2); (C) J-ATLL EP300Mut cells (J1); (D) NA-ATLL EP300WT cells (NA1); (E) NA-ATLL EP300Mut (NA2) cells; (F) NA-ATLL EP300WT treated with 500 nM JQAD1 for 48 h. The yellow arrows indicate the sites along the molecules where the IdU transitioned to CldU. The molecules are arranged in the following order: molecules with initiation events, molecules with 3’ to 5’ travelling forks, molecules with 5’ to 3’ travelling forks, and molecules with termination events. G Percentage of molecules with initiation sites in FRA6E in J-ATLL EP300WT, J-ATLL EP300Mut, NA-ATLL EP300WT, NA-ATLL EP300Mut and NA-ATLL EP300WT cells + 500nMJQAD1 (48 h), N = 2. Data are presented as mean values +/− SD. P-values were determined by a two-tailed, Student T-test. The p-values are indicated as follows: * <0.03, ** <0.0021. Source data are provided as a Source Data file.