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. Author manuscript; available in PMC: 2010 Nov 22.
Published in final edited form as: Genes Cancer. 2010 Jul 1;1(7):787–796. doi: 10.1177/1947601910382774

Figure 1.

Figure 1

The DDR pathway. In response to DNA DSBs, ATM and related PIKKs phosphorylate H2AX (γH2AX), creating a platform for the assembly of DDR proteins. Localization of MDC1 to sites of damage by binding to γH2AX and its subsequent phosphorylation by ATM is required for the recruitment of the ubiquitin E3 ligase RNF8. RNF8, together with the E2 ubiquitin conjugating enzyme Ubc13 and HERC2, synthesize K63-linked ubiquitin on histone H2A and its variants. RNF168, another RING domain ubiquitin ligase, recognizes the ubiquitin conjugates synthesized by RNF8/Ubc13, leading to its recruitment to sites of damage and further synthesis of K63-linked ubiquitin. RAP80 specifically binds to K63-linked ubiquitin, recruiting a protein complex including Abraxas, MERIT40, BRCC36, BRCC45 and BRCA1 to sites of damage.