| 背景 | DNA oxidative demethylase ALKBH2 is a ~29 kDa protein. Dioxygenase that repairs alkylated nucleic acid bases by direct reversal oxidative dealkylation. Can process both double-stranded (ds) and single-stranded (ss) DNA substrates, with a strong preference for dsDNA. Uses molecular oxygen, 2-oxoglutarate and iron as cofactors to oxidize the alkyl groups that are subsequently released as aldehydes, regenerating the undamaged bases. Probes the base pair stability, locates a weakened base pair and flips the damaged base to accommodate the lesion in its active site for efficient catalysis. Repairs monoalkylated bases, specifically N1-methyladenine and N3-methylcytosine, as well as higher order alkyl adducts such as bases modified with exocyclic bridged adducts known as etheno adducts including 1,N6-ethenoadenine, 3,N4-ethenocytosine and 1,N2-ethenoguanine. 1. Duncan, T. et al. (2002) Proceedings of the National Academy of Sciences of the United States of America 99, 16660-5. PMID: 124862303. Lee, DH. et al. (2005) The Journal of biological chemistry 280, 39448-59. PMID: 161747694. Chen, B. et al. (2010) Molecular bioSystems 6, 2143-9. PMID: 207145068. Yi, C. et al. (2012) Nature structural & molecular biology 19, 671-6. PMID: 22659876 |
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