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'''HUMAN APURINIC/APYRIMIDINIC ENDONUCLEASE-1 (APE1) BOUND TO ABASIC DNA''' | '''HUMAN APURINIC/APYRIMIDINIC ENDONUCLEASE-1 (APE1) BOUND TO ABASIC DNA''' | ||
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==Reference== | ==Reference== | ||
DNA-bound structures and mutants reveal abasic DNA binding by APE1 and DNA repair coordination [corrected], Mol CD, Izumi T, Mitra S, Tainer JA, Nature. 2000 Jan 27;403(6768):451-6. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10667800 10667800] | DNA-bound structures and mutants reveal abasic DNA binding by APE1 and DNA repair coordination [corrected], Mol CD, Izumi T, Mitra S, Tainer JA, Nature. 2000 Jan 27;403(6768):451-6. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10667800 10667800] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: Mol, C D.]] | [[Category: Mol, C D.]] | ||
[[Category: Tainer, J A.]] | [[Category: Tainer, J A.]] | ||
[[Category: | [[Category: Abasic site]] | ||
[[Category: | [[Category: Dna repair]] | ||
[[Category: | [[Category: Enzyme:dna complex]] | ||
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Revision as of 13:45, 2 May 2008
HUMAN APURINIC/APYRIMIDINIC ENDONUCLEASE-1 (APE1) BOUND TO ABASIC DNA
OverviewOverview
Non-coding apurinic/apyrimidinic (AP) sites in DNA are continually created in cells both spontaneously and by damage-specific DNA glycosylases. The biologically critical human base excision repair enzyme APE1 cleaves the DNA sugar-phosphate backbone at a position 5' of AP sites to prime DNA repair synthesis. Here we report three co-crystal structures of human APE1 bound to abasic DNA which show that APE1 uses a rigid, pre-formed, positively charged surface to kink the DNA helix and engulf the AP-DNA strand. APE1 inserts loops into both the DNA major and minor grooves and binds a flipped-out AP site in a pocket that excludes DNA bases and racemized beta-anomer AP sites. Both the APE1 active-site geometry and a complex with cleaved AP-DNA and Mn2+ support a testable structure-based catalytic mechanism. Alanine substitutions of the residues that penetrate the DNA helix unexpectedly show that human APE1 is structurally optimized to retain the cleaved DNA product. These structural and mutational results show how APE1 probably displaces bound glycosylases and retains the nicked DNA product, suggesting that APE1 acts in vivo to coordinate the orderly transfer of unstable DNA damage intermediates between the excision and synthesis steps of DNA repair.
About this StructureAbout this Structure
1DE8 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
DNA-bound structures and mutants reveal abasic DNA binding by APE1 and DNA repair coordination [corrected], Mol CD, Izumi T, Mitra S, Tainer JA, Nature. 2000 Jan 27;403(6768):451-6. PMID:10667800 Page seeded by OCA on Fri May 2 13:45:13 2008