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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

Lookup NU author(s): Dr Javier Abellon-Ruiz, Professor Bernard Connolly

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

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.


Publication metadata

Author(s): Abellon-Ruiz J, Ishino S, Ishino Y, Connolly BA

Publication type: Article

Publication status: Published

Journal: Archaea

Year: 2016

Volume: 2016

Online publication date: 19/09/2016

Acceptance date: 01/08/2016

Date deposited: 13/12/2016

ISSN (print): 1472-3646

ISSN (electronic): 1472-3654

Publisher: Hindawi Publishing Corporation

URL: http://dx.doi.org/10.1155/2016/1510938

DOI: 10.1155/2016/1510938


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