Extended presence of AID in the nucleus causes more mutations. (A) Relative mutation rates at 5′-Sμ, AID off-target sites (Cd83, Pax5, Apobec3, Ly6e, and Il4ra), and non-AID targets (Cμ, Cγ1, and Cd3e), revealed by MutPE-Seq. *, P < 0.05; **, P < 0.01, one-tailed bootstrap test. Two independent experiments were performed. (B) Proposed model. AID induces deamination at the Igh gene only during a short time window in early G1. Before then, although AID has spatial contact with chromosomes after breakdown of the nuclear envelope (NE), chromosomal DNA is condensed and not available for deamination. Shortly thereafter, AID is quickly exported into the cytoplasm by Crm1-mediated nuclear export. During the rest of the cell cycle, AID is cytoplasmic and no significant AID activity is detected. Therefore, this limited time window for AID to induce deamination is the combined consequence of transient nuclear residence of AID and the recovered transcription in the early G1 phase. The AID-induced uracil in this short time period is processed in G1 to enable SHM and CSR.