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. 2020 Mar 31;23(4):101027. doi: 10.1016/j.isci.2020.101027

Figure 6.

Figure 6

Proposed Model for Ten-Step Elimination of the Adducts Attached to DSB Ends

(A) Restriction enzyme generates “clean” DSBs with 3′- hydroxyl groups and 5′-phosphate ends (step 1). The DSB ends are rapidly recognized by the KU70/80 complex (step 2) and rejoined by canonical NHEJ (step 3).

(B) Ionizing radiation generates “dirty” DSBs associated with 3′ and 5′ adducts (step 1). The DSB ends are rapidly recognized by the KU70/80 complex (step 2). UBC13 promotes K63 ubiquitination at DSB sites (step 3), where this ubiquitination is recognized by the BRCA1-RAP80 complex (step 4). UBC13 and RAP80 are required for stable complex formation between BRCA1 and MRE11 at DSB sites (step 5). Endonucleolytic cleavage by MRE11 releases 5′ and -3′ adducts from the DSB ends (steps 6–8). The resulting clean DSB ends are again recognized by the KU70/80 complex (step 9), then ligated by canonical NHEJ (step 10).