Fig. 3: The BCDX2 structure reveals a RAD51C variant cluster in the Walker B region.

a Linear schematic of RAD51C ovarian cancer variants with functional data for HR proficiency by SCR assay (circle), interaction with RAD51D by yeast-three-hybrid (Y3H, square), and sensitivity to olaparib and cisplatin (triangle). Note that the functional data from the starred (*) residues are from this study whereas the unstarred residues were previously reported in Prakash et al. and diagrammed here for direct comparison¹². Variants sensitive to olaparib and cisplatin are indicated in red whereas insensitive variants are indicated in green. HR proficient variants are indicated in green (60–100%), intermediate variants are in yellow (40–59%), and deficient variants are in red (0–39%). The Walker A motif is indicated with a purple box, the Walker B motif with a gold box, the DNA binding loops in blue boxes and the NLS with a light blue box. b CryoEM structure of the BCDX2 complex with ssDNA (PDB ID:8GBJ). The sites highlighted in this study are labeled in black. c Domain organization and binding interfaces of RAD51C with RAD51D, DNA, RAD51B, and ATP binding pocket in the complex. In each case, the HR efficiency of the variant shown in (a) is indicated in red (deficient), yellow (intermediate), or green (proficient, with corresponding colored text. d Site I: The critical residues near the Walker B motif; Site II: RAD51C residues which are present near the ATP binding pocket and RAD51D interaction interface. Site III: RAD51C residues which are present near RAD51B. Site IV: N-terminal residues of RAD51C which are present on the RAD51D interaction interface. In each case, HR efficiency of the variant shown in (a) is indicated in red (deficient), yellow (intermediate), or green (proficient), with corresponding colored text.