Fig. 7

AUNIP is required for genome stability and cellular resistance to DSB-inducing agents. a Wild-type or AUNIP-deficient HeLa cells were either mock treated or treated with 40 μM CPT for 12 h. Metaphase spreads were then prepared following standard procedures. Representative images are shown in a. Arrows indicate chromosome aberrations. Quantification of chromosomal aberrations from indicated cells is shown in b. Data represent the average for two independent experiments. At least 50 metaphases were counted in each experiment. c–f Sensitivity of wild-type cells or AUNIP-deficient HeLa cells to CPT, Topotecan, ABT-888, or IR was determined by a colony formation assay. Data represent means ± SEM from three independent experiments. g CPT sensitivity of wild-type or AUNIP-deficient cells that stably express empty vector (Vector), wild-type AUNIP, the Δ25–70 mutant, or the 1–280 mutant was determined by a colony formation assay. Data represent means ± SEM from three independent experiments. h Working model depicting a proposed role of AUNIP in DSB repair choice. Left panel: Noting that AUNIP displays low affinities for dsDNA ends, most of the two-ended DSBs are recognized and are repaired by the NHEJ machinery. Right panel: AUNIP enhances CtIP tethering at perturbed replication forks and directs replication-associated one-ended DSBs toward the HR repair pathway