Structure of the ubiquitin-binding zinc finger domain of human DNA Y-polymerase Z

The ubiquitin-binding zinc finger (UBZ) domain of human DNA Y-family polymerase (pol) g is important in the recruitment of the polymerase to the stalled replication machinery in translesion synthesis. Here, we report the solution structure of the pol g UBZ domain and its interaction with ubiquitin. We show that the UBZ domain adopts a classical C2H2 zinc-finger structure characterized by a bba fold. Nuclear magnetic resonance titration maps the binding interfaces between UBZ and ubiquitin to the a-helix of the UBZ domain and the canonical hydrophobic surface of ubiquitin defined by residues L8, I44 and V70. Although the UBZ domain binds ubiquitin through a single a-helix, in a manner similar to the inverted ubiquitin-interacting motif, its structure is distinct from previously characterized ubiquitin-binding domains. The pol g UBZ domain represents a novel member of the C2H2 zinc finger family that interacts with ubiquitin to regulate translesion synthesis.