Structural basis for recognition and repair of the 3'-phosphate by NExo, a base excision DNA repair nuclease from Neisseria meningitidis

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Title: Structural basis for recognition and repair of the 3'-phosphate by NExo, a base excision DNA repair nuclease from Neisseria meningitidis
Authors: Silhan, J
Zhao, Q
Boura, E
Thomson, H
Förster, A
Tang, CM
Freemont, PS
Baldwin, GS
Item Type: Journal Article
Abstract: NExo is an enzyme from Neisseria meningitidis that is specialized in the removal of the 3'-phosphate and other 3'-lesions, which are potential blocks for DNA repair. NExo is a highly active DNA 3'-phosphatase, and although it is from the class II AP family it lacks AP endonuclease activity. In contrast, the NExo homologue NApe, lacks 3'-phosphatase activity but is an efficient AP endonuclease. These enzymes act together to protect the meningococcus from DNA damage arising mainly from oxidative stress and spontaneous base loss. In this work, we present crystal structures of the specialized 3'-phosphatase NExo bound to DNA in the presence and absence of a 3'-phosphate lesion. We have outlined the reaction mechanism of NExo, and using point mutations we bring mechanistic insights into the specificity of the 3'-phosphatase activity of NExo. Our data provide further insight into the molecular origins of plasticity in substrate recognition for this class of enzymes. From this we hypothesize that these specialized enzymes lead to enhanced efficiency and accuracy of DNA repair and that this is important for the biological niche occupied by this bacterium.
Issue Date: 14-Dec-2018
Date of Acceptance: 12-Oct-2018
URI: http://hdl.handle.net/10044/1/65533
DOI: https://dx.doi.org/10.1093/nar/gky934
ISSN: 0305-1048
Publisher: Oxford University Press
Start Page: 11980
End Page: 11989
Journal / Book Title: Nucleic Acids Research
Volume: 46
Issue: 22
Copyright Statement: © The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http: // creativecommons.org / licenses / by-nc / 4.0 / ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
Keywords: 05 Environmental Sciences
06 Biological Sciences
08 Information And Computing Sciences
Developmental Biology
Publication Status: Published
Conference Place: England
Online Publication Date: 2018-10-17
Appears in Collections:Department of Medicine
Faculty of Medicine



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