FIGURE 2.
The types of events resulting from interstitial and telomeric I-SceI-induced DSBs. DSB repair at interstitial sites occurs primarily by C-NHEJ, although some DSBs are also repaired by HRR, involving error-free repair, and A-NHEJ, which is associated with large deletions and GCRs. Direct ligation of the ends of DSBs without the loss of the I-SceI site by C-NHEJ is the most common event at interstitial DSBs. Small deletions of a few base pairs that eliminate the I-SceI site are the next most common event, followed by HRR, large deletions, and GCRs. The deficiency in NHEJ near telomeres is proposed to be due to inhibition of C-NHEJ, while the efficiency of HRR is unchanged. As a result, most DSBs near telomeres are repaired by A-NHEJ. Consistent with a predominant role for A-NHEJ in repair of telomeric DSBs, large deletions are the most common event at I-SceI-induced DSBs near telomeres. Most of these large deletions would also result in GCRs, because they cause the loss of the telomere. GCRs that occur without large deletions are also greatly increased at DSBs near telomeres, while small deletions of a few base pairs occur at the same frequency as at interstitial DSBs.