Crystal structure of the SLF1 tandem BRCT domains in complex with a RPB2-derived peptide

The tandem BRCT domains in the SMC5/6 complex localization factor 1 (SLF1, SLF1^tBRCT) mediate interactions with a phosphorylated region in Rad18 and interaction targets the SMC5/6 complex to DNA damage sites for repair. Whether SLF1^tBRCT mediate interactions with additional proteins is unclear. In this study, we searched for novel SLF1^tBRCT binding partners and found that RNA polymerase II subunit 2 (RPB2) may contain a SLF1^tBRCT binding site. The crystal structure of SLF1^tBRCT in complex with a RPB2 peptide containing the predicted binding site revealed a SLF1^tBRCT-RPB2 interface that bares similarity to the previously reported SLF1^tBRCT-Rad18 interface but contains several unique features. Importantly, the SLF1^tBRCT BRCT2 domain undergoes conformational changes to accommodate the C-terminus of the RPB2 peptide. Interestingly, this domain also mediates domain-swapping interactions between neighboring SLF1^tBRCT molecules in the crystal. Our study suggests that RPB2 may be a potential SLF1 binding partner and provides insights into the structural flexibility of SLF1^tBRCT.