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.
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.
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DOI：
10.1155/2016/1510938
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Connolly BA
中科院分区：
文献类型：
--
作者：
Abellón-Ruiz J;Ishino S;Ishino Y;Connolly BA
在古细菌中，尿嘧啶和次黄嘌呤的修复分别由胞嘧啶和腺嘌呤的脱氨基作用产生，由三种酶启动：尿嘧啶-DNA-糖基化酶（UDG，识别尿嘧啶）；核酸内切酶 V（EndoV，识别次黄嘌呤）；和核酸内切酶 Q (EndoQ)（可识别尿嘧啶和次黄嘌呤）。两种古细菌 DNA 聚合酶 Pol-B 和 Pol-D 受到模板链中脱氨基碱基的抑制，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。这里证明，Pol-D 与含有脱氨基碱基的引物模板的结合会抑制 UDG、EndoV 和 EndoQ 的活性。同样，Pol-B 几乎完全关闭 EndoQ，延续了早期的工作，证明 Pol-B 减少了 UDG 和 EndoV 的催化作用。与 Pol-D 相比，Pol-B 被认为是更有效的酶抑制剂。尽管 Pol-D 直接被模板链尿嘧啶抑制，但 Pol-B 的存在进一步将 Pol-D 的任何残留活性抑制至接近于零的水平。结果与 Pol-D 作为复制聚合酶和 Pol-B 主要作为防止脱氨基碱基诱导的 DNA 突变的守护者的功能相一致。
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.
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影响因子：
5.6
作者：
Firbank, Susan J.;Wardle, Josephine;Connolly, Bernard A.
通讯作者：
Connolly, Bernard A.
DOI：
10.1073/pnas.95.24.14250
发表时间：
1998-11-24
影响因子：
11.1
作者：
Cann, IKO;Komori, K;Ishino, Y
通讯作者：
Ishino, Y
影响因子：
4.8
作者：
Lee, Hyun-Wook;Dominy, Brian N.;Cao, Weiguo
通讯作者：
Cao, Weiguo
影响因子：
5.6
作者：
Emptage, Kieran;O'Neill, Rory;Connolly, Bernard A.
通讯作者：
Connolly, Bernard A.
影响因子：
14.9
作者：
Richardson TT;Gilroy L;Ishino Y;Connolly BA;Henneke G
通讯作者：
Henneke G