The crystal structure of the human DNA repair endonuclease HAP1 suggests the recognition of extra‐helical deoxyribose at DNA abasic sites
Michael A. Gorman,Solange Moréra,Dominic G. Rothwell,Eric de La Fortelle,Clifford D. Mol,John A. Tainer,Ian D. Hickson,Paul S. Freemont +7 more
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The HAP1 structure suggests a mechanism for AP site binding which involves the recognition of the deoxyribose moiety in an extra‐helical conformation, rather than a ‘flipped‐out’ base opposite the AP site.Abstract:
The structure of the major human apurinic/ apyrimidinic endonuclease (HAP1) has been solved at 2.2 A resolution. The enzyme consists of two symmetrically related domains of similar topology and has significant structural similarity to both bovine DNase I and its Escherichia coli homologue exonuclease III (EXOIII). A structural comparison of these enzymes reveals three loop regions specific to HAP1 and EXOIII. These loop regions apparently act in DNA abasic site (AP) recognition and cleavage since DNase I, which lacks these loops, correspondingly lacks AP site specificity. The HAP1 structure furthermore suggests a mechanism for AP site binding which involves the recognition of the deoxyribose moiety in an extrahelical conformation, rather than a 'flipped-out' base opposite the AP site.read more
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