Department of Biology, Massachusetts Institute of Technology, Cambridge, 02139, USA.
DNA Repair (Amst). 2010 Nov 10;9(11):1130-41. doi: 10.1016/j.dnarep.2010.08.001. Epub 2010 Sep 15.
Recent research has revealed the presence of ubiquitin-binding domains in the Y family polymerases. The ubiquitin-binding zinc finger (UBZ) domain of human polymerase η is vital for its regulation, localization, and function. Here, we elucidate structural and functional features of the non-canonical UBZ motif of Saccharomyces cerevisiae pol η. Characterization of pol η mutants confirms the importance of the UBZ motif and implies that its function is independent of zinc binding. Intriguingly, we demonstrate that zinc does bind to and affect the structure of the purified UBZ domain, but is not required for its ubiquitin-binding activity. Our finding that this unusual zinc finger is able to interact with ubiquitin even in its apo form adds support to the model that ubiquitin binding is the primary and functionally important activity of the UBZ domain in S. cerevisiae polymerase η. Putative ubiquitin-binding domains, primarily UBZs, are identified in the majority of known pol η homologs. We discuss the implications of our observations for zinc finger structure and pol η regulation.
最近的研究揭示了 Y 家族聚合酶中存在泛素结合结构域。人类聚合酶 η 的泛素结合锌指（UBZ）结构域对其调节、定位和功能至关重要。在这里，我们阐明了酿酒酵母 pol η 中非典型 UBZ 基序的结构和功能特征。pol η 突变体的特性证实了 UBZ 基序的重要性，并暗示其功能不依赖于锌结合。有趣的是，我们证明锌确实结合并影响纯化的 UBZ 结构域的结构，但不是其泛素结合活性所必需的。我们的发现表明，这种不寻常的锌指即使在apo 形式下也能够与泛素相互作用，这为泛素结合是酿酒酵母聚合酶 η UBZ 结构域的主要和功能上重要的活性的模型提供了支持。在大多数已知的 pol η 同源物中都鉴定出了假定的泛素结合结构域，主要是 UBZs。我们讨论了我们的观察结果对锌指结构和 pol η 调节的影响。
