Increased ISR in Fanca^−/− mice. (A) A model for the joining of AID-generated DSBs between S regions during switch to IgG1. AID generates multiple DSBs within a given S region, and CSR joins two DSBs from two different S regions, producing canonical Sµ-Sγ1 junctions. The intervening double-stranded DNA fragments are then degraded or joined to form excision circles; occasionally some rejoined sequences exhibiting unusual junctions (e.g., Sµ-Sµ-Sγ1 or Sµ-Sγ1-Sγ1) resulting from local rejoining or ISR are observed. (B) Frequency of ISR in WT and Fanca^−/− B cells induced to switch to IgG1 by anti-CD40 and IL-4 for 4 d. ISR was examined by analysis of Sμ-Sγ1 junctions. Horizontal bars indicate the means (*, P < 0.05 with the two-tailed Student’s t test). (C) Bar graph shows the percentage of Sμ and Sγ1 ISR in WT and Fanca^−/− B cells from B. (D) Percentage of sequences exhibiting blunt joins (0), indicated MH, or insertions at the ISR junction. Data for the ISR analysis are based on five mice per genotype from five independent experiments.