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. Author manuscript; available in PMC: 2017 Oct 20.
Published in final edited form as: Mol Cell. 2016 Oct 6;64(2):376–387. doi: 10.1016/j.molcel.2016.09.005

Figure 7. Working Model for Dynamic Lesion Recognition by Rad4-Rad23.

Figure 7

(A) Domains of Rad4-Rad23 (PDB: 2QSF) color-coded as shown in (B): TGD – yellow, BHD1 – pink, BHD2 – cyan, BHD3 – blue, Rad23 – green.

(B) Rad4-Rad23 scans DNA through 3D or 1D diffusion (i) and tests integrity of DNA via bending/twisting during 1D diffusion on DNA (ii). Depending on the type of damage encountered, Rad4-Rad23 can either undergo constrained motion around lesion due to lack of β-hairpin 3 insertion (iiia), or alternatively rapidly forms stable protein-DNA complex at site of lesion with β-hairpin 3 inserted for stabilization in a twist-open action (Velmurugu et al., 2016) (iiib). While it is possible that the DNA in (iiia) is bent, for simplicity this is not shown. Extra time spent probing the lesion, afforded by constrained motion of Rad4-Rad23, could also lead to stable binding of the protein at sites that require larger base opening/flipping energies (iv).