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Structural basis for the recognition and cleavage of abasic DNA in Neisseria meningitidis

DOI: 10.1073/pnas.1206563109 DOI Help
PMID: 23035246 PMID Help

Authors: Duo Lu (Imperial College London) , Jan Silhan (Imperial College London) , James T. Macdonald (Imperial College London) , Elisabeth P. Carpenter (Imperial College London) , Kirsten Jensen (Imperial College London) , Christoph M. Tang (Imperial College London) , Geoff S. Baldwin (Imperial College London) , Paul S. Freemont (Imperial College London)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Proceedings Of The National Academy Of Sciences , VOL 109 (42) , PAGES 16852 - 16857

State: Published (Approved)
Published: October 2012

Abstract: Base excision repair (BER) is a highly conserved DNA repair pathway throughout all kingdoms from bacteria to humans. Whereas several enzymes are required to complete the multistep repair process of damaged bases, apurinic-apyrimidic (AP) endonucleases play an essential role in enabling the repair process by recognizing intermediary abasic sites cleaving the phosphodiester backbone 5? to the abasic site. Despite extensive study, there is no structure of a bacterial AP endonuclease bound to substrate DNA. Furthermore, the structural mechanism for AP-site cleavage is incomplete. Here we report a detailed structural and biochemical study of the AP endonuclease from Neisseria meningitidis that has allowed us to capture structural intermediates providing more complete snapshots of the catalytic mechanism. Our data reveal subtle differences in AP-site recognition and kinetics between the human and bacterial enzymes that may reflect different evolutionary pressures.

Journal Keywords: X-Ray; DNA; DNA; DNA-(Apurinic; Furans; Humans; Models; Molecular; Neisseria; Protein; Protein Folding

Subject Areas: Biology and Bio-materials


Instruments: I03-Macromolecular Crystallography , I04-Macromolecular Crystallography

Other Facilities: Daresbury 10.1

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