J. Abellón-Ruiz, S. Ishino, Y. Ishino, B. Connolly
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引用次数: 4
摘要
在古细菌中,尿嘧啶和次黄嘌呤分别由胞嘧啶和腺嘌呤脱胺作用产生,它们的修复是由三种酶启动的:尿嘧啶- dna -糖基化酶(UDG,识别尿嘧啶);内切酶V (EndoV,识别次黄嘌呤);和内切酶Q (EndoQ)(它能识别尿嘧啶和次黄嘌呤)。两个古细菌DNA聚合酶,Pol-B和Pol-D,被模板链中的脱胺碱基抑制,这是该结构域独有的特征。因此,三种修复酶和两种聚合酶对尿嘧啶和次黄嘌呤表现出重叠的特异性。结果表明,Pol-D与含有脱胺碱基的引物模板结合可抑制UDG、EndoV和EndoQ的活性。类似地,Pol-B几乎完全关闭了EndoQ,扩展了早期的工作,证明Pol-B降低了UDG和EndoV的催化作用。与Pol-D相比,Pol-B是一种更有效的酶抑制剂。尽管Pol-D被模板链尿嘧啶直接抑制,但Pol-B的存在进一步抑制了Pol-D的残留活性,使其接近于零水平。结果与Pol-D作为复制聚合酶和Pol-B主要作为防止脱胺碱基诱导的DNA突变的守护者相一致。
Archaeal DNA Polymerase-B as a DNA Template Guardian: Links between Polymerases and Base/Alternative Excision Repair Enzymes in Handling the Deaminated Bases Uracil and Hypoxanthine
In Archaea repair of uracil and hypoxanthine, which arise by deamination of cytosine and adenine, respectively, is initiated by three enzymes: Uracil-DNA-glycosylase (UDG, which recognises uracil); Endonuclease V (EndoV, which recognises hypoxanthine); and Endonuclease Q (EndoQ), (which recognises both uracil and hypoxanthine). Two archaeal DNA polymerases, Pol-B and Pol-D, are inhibited by deaminated bases in template strands, a feature unique to this domain. Thus the three repair enzymes and the two polymerases show overlapping specificity for uracil and hypoxanthine. Here it is demonstrated that binding of Pol-D to primer-templates containing deaminated bases inhibits the activity of UDG, EndoV, and EndoQ. Similarly Pol-B almost completely turns off EndoQ, extending earlier work that demonstrated that Pol-B reduces catalysis by UDG and EndoV. Pol-B was observed to be a more potent inhibitor of the enzymes compared to Pol-D. Although Pol-D is directly inhibited by template strand uracil, the presence of Pol-B further suppresses any residual activity of Pol-D, to near-zero levels. The results are compatible with Pol-D acting as the replicative polymerase and Pol-B functioning primarily as a guardian preventing deaminated base-induced DNA mutations.
期刊介绍:
Archaea is a peer-reviewed, Open Access journal that publishes original research articles as well as review articles dealing with all aspects of archaea, including environmental adaptation, enzymology, genetics and genomics, metabolism, molecular biology, molecular ecology, phylogeny, and ultrastructure. Bioinformatics studies and biotechnological implications of archaea will be considered. Published since 2002, Archaea provides a unique venue for exchanging information about these extraordinary prokaryotes.