Files in this Data Supplement:
- Document 1. Supplemental methods, tables, and figures (PDF, 915 KB)
- Video 1. Computer modeling of the interaction of aptamer F79 with RAD52 protomers (MOV, 9.8 MB) - We extracted three chains (A, B and K) from the undecameric crystal structure of the N-terminal annealing domain of human RAD52 and then cut away the middle chain A to reveal the location of the 13 residues in chain B corresponding to the F79 aptamer (Figure 3B). The 13 residues make up part of the monomer-monomer binding interface <sup>21,22</sup>. Modeling of the F79 aptamer suggests that it can mimic these 13 residues and bind to the neighboring subunit, thereby blocking the binding of one monomer to the other. The size of the buried surface area of the F79 aptamer (530 Å<sup>2</sup>) appears adequate to affect disruption of the protein-protein interaction represented by monomer-monomer binding (buried surface area = approximately 2,600 Å<sup>2</sup>). In addition, a number of favorable binding interactions between the F79 aptamer and the RAD52 subunit were identified by interface analysis, including a key interaction between the aptamer tyrosine corresponding to Y81 and the natural Y81 binding pocket on the neighboring subunit <sup>23</sup>. In this model, the aptamer phenylalanine residue corresponding to F79 protrudes out into the binding domain and cannot be accommodated by the opposing subunit face. This bulky benzyl group may play a significant role in prohibiting subunit binding, thus reducing ssDNA binding by preventing or destabilizing the oligomeric assembly of RAD52.