ATR and DNA-PK_cs prevent viral genome concatemer formation when ATM is inhibited.

<p>(A) Southern blot of DNA extracted from SV40-infected BSC40 cells treated with combinations of DMSO, ATRi, ATMi, and/or Nu7026 during the final 28 h of a 48 h infection. The middle panel shows a longer exposure of a portion of the Southern blot pictured in the top panel. To emphasize SV40 replication intermediates and aberrant products, equal amounts of total SV40 DNA were loaded into each lane. (B) Quantification of monomer accumulation when PIKK(s) are inhibited from Southern blots as shown in (A). (C) Graph of total viral or SV40 monomer DNA signals normalized to SV40 DNA replicated in the presence of DMSO from Southern blots as shown in (A). (D) Graph of aberrant structure(s) accumulated as a result of single or multiple PIKK inhibition from Southern blots as shown in (A). In (B–D), bars for DMSO, ATRi, and ATMi show the average of 6 to 7 independent experiments. In the same panels, the bar for Nu-7026 shows the average of 4 independent experiments; whereas bars for combinations of inhibitors (ATMi/ATRi, Nu7026/ATRi, and ATMi/Nu7026) show the average of 3 independent experiments.