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. Author manuscript; available in PMC: 2023 Jul 1.
Published in final edited form as: Trends Biochem Sci. 2022 Mar 26;47(7):582–595. doi: 10.1016/j.tibs.2022.03.001

Figure 5. Nucleosome-based recruitment and activity of BRCA1/BARD1 in DNA DSB repair.

Figure 5.

(A) Schematic of BRCA1/BARD1 and 53BP1 recruitment pathways and retention at damaged chromatin. The left two pathways are reliant on RNF168-mediated H2A K15-Ub, while the right pathway (separated by dashed line) is reliant on RNF8-mediated K63-linked poly-Ub deposited on linker histone H1. The center pathway reliant on H2A K15-Ub and H4K20me0 requires the BRCA1 RING domain and ligase proficiency for DSB site retention and HR, indicated by the curved arrow with an asterisk. (B) Schematic of BRCA1/BARD1-dependent H2A-Ub activity in the DNA end-resection step of HR. BRCA1/BARD1 is recruited to DSB sites and ubiquitylates H2A K127 (1, top). HR is licensed through limited end-resection of broken DNA ends via association of BRCA1/BARD1 with CtIP and MRN (1 and 2, top and middle, light green arrow). SMARCAD1 is recruited via BRCA1/BARD1-dependent H2A K127-Ub, excludes the NHEJ factor 53BP1 from break sites, and performs ATP-dependent nucleosome repositioning to facilitate long-range DNA end-resection (2, middle). This is antagonized by the action of the deubiquitylating enzyme USP48, which specifically removes H2A K127-Ub to prevent over-resected DNA tracts and facilitate HR (3, bottom). Question marks in panels denote unknown interactions (A) or speculative complexes (B).