Showalter A K, Byeon I J, Su M I, Tsai M D
Department of Chemistry, The Ohio State University, Columbus Ohio 43210, USA.
Nat Struct Biol. 2001 Nov;8(11):942-6. doi: 10.1038/nsb1101-942.
The African swine fever virus DNA polymerase X (ASFV Pol X or Pol X), the smallest known nucleotide polymerase, has recently been reported to be an extremely low fidelity polymerase that may be involved in strategic mutagenesis of the viral genome. Here we report the solution structure of Pol X. The structure, unique within the realm of nucleotide polymerases, consists of only palm and fingers subdomains. Despite the absence of a thumb subdomain, which is important for DNA binding in other polymerases, we show that Pol X binds DNA with very high affinity. Further structural analyses suggest a novel mode of DNA binding that may contribute to low fidelity synthesis. We also demonstrate that the ASFV DNA ligase is a low fidelity ligase capable of sealing a nick that contains a G-G mismatch. This supports the hypothesis of a virus-encoded, mutagenic base excision repair pathway consisting of a tandem Pol X/ligase mutator.
非洲猪瘟病毒DNA聚合酶X（ASFV Pol X或Pol X）是已知最小的核苷酸聚合酶，最近有报道称它是一种极低保真度的聚合酶，可能参与病毒基因组的策略性诱变。在此我们报道了Pol X的溶液结构。该结构在核苷酸聚合酶领域独一无二，仅由手掌和手指亚结构域组成。尽管缺少对其他聚合酶中DNA结合很重要的拇指亚结构域，但我们发现Pol X以非常高的亲和力结合DNA。进一步的结构分析表明了一种可能导致低保真度合成的新型DNA结合模式。我们还证明了ASFV DNA连接酶是一种低保真度连接酶，能够封闭含有G-G错配的切口。这支持了由串联的Pol X/连接酶诱变剂组成的病毒编码诱变碱基切除修复途径的假说。
