FIGURE 3.

Model for processing DSBs near telomeres. The presence of TRF2 at the telomere (red horizontal lines) promotes chromosome healing by inhibiting ATM, which is required to activate PIF1 and/or other redundant proteins that prevent chromosome healing by binding to TERT, the catalytic subunit of telomerase. TRF2 also promotes the inappropriate processing of DSBs near telomeres by Apollo, which is then followed by extensive resection by EXO1. This function of Apollo is normally involved in the generation of single-stranded 3′ overhangs required for telomere formation. However, unlike telomeres (red horizontal lines), in which resection is limited by POT1/TPP1 binding to the single-stranded telomeric DNA, resection of DSBs in subtelomeric regions (black horizontal lines) continues unabated due to the inability of POT1/TPP1 to bind to non-telomeric DNA. The inappropriate processing of the DSB results in large deletions and/or GCRs with other chromosomes (green horizontal lines) through a mechanism involving A-NHEJ.