3s5a
ABH2 cross-linked to undamaged dsDNA-2 with cofactorsABH2 cross-linked to undamaged dsDNA-2 with cofactors
Structural highlights
Publication Abstract from PubMedALKBH2 is a direct DNA repair dioxygenase guarding the mammalian genome against N(1)-methyladenine, N(3)-methylcytosine and 1,N(6)-ethenoadenine damage. A prerequisite for repair is to identify these lesions in the genome. Here we present crystal structures of human ALKBH2 bound to different duplex DNAs. Together with computational and biochemical analyses, our results suggest that DNA interrogation by ALKBH2 has two previously unknown features: (i) ALKBH2 probes base-pair stability and detects base pairs with reduced stability, and (ii) ALKBH2 does not have nor need a damage-checking site, which is critical for preventing spurious base cleavage for several glycosylases. The demethylation mechanism of ALKBH2 insures that only cognate lesions are oxidized and reversed to normal bases, and that a flipped, non-substrate base remains intact in the active site. Overall, the combination of duplex interrogation and oxidation chemistry allows ALKBH2 to detect and process diverse lesions efficiently and correctly. Duplex interrogation by a direct DNA repair protein in search of base damage.,Yi C, Chen B, Qi B, Zhang W, Jia G, Zhang L, Li CJ, Dinner AR, Yang CG, He C Nat Struct Mol Biol. 2012 Jun 3;19(7):671-6. doi: 10.1038/nsmb.2320. PMID:22659876[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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