(A-C) Clonogenic cell survival assays detect effects of EXO5 and/or BLM depletion on drug sensitivity of HeLa cells against HU, cisplatin, and CPT. Data presented as interpolated from three independent experiments (* p<0.05, ** p<0.01, student t test) (D-E) DNA fiber analysis determining replication fork recovery in EXO5 and/or BLM depleted cells with HU or cisplatin treatment (****p<0.0001, Mann-Whitney test). (F-I) Clonogenic cell survival to detect effect of depletion of MUS81, DNA2, MRE11, and EXO1 depletion and with or without EXO5 KD after HU treatment. (J) Western blot with noted antibodies show efficient KD. (K) DNA fiber analysis to determine DNA replication fork recovery in HeLa cell depleted for proteins as indicated with HU treatment. (L) The rhq1Δ exo5Δ double mutant resembles growth rate in the single mutants by tetrad dissection assay. (M) EXO5 end-resection on replication fork mimic substrate with BLMcat and RPA70NAB. Reaction mixture incubated at 30 °C for 30 min. (Cy5-labeled at 3’-end, star). See Figure S5.