Direct repair of 3,N(4)-ethenocytosine by the human ALKBH2 dioxygenase is blocked by the AAG/MPG glycosylase.
Direct repair of 3,N(4)-ethenocytosine by the human ALKBH2 dioxygenase is blocked by the AAG/MPG glycosylase.
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DOI：
10.1016/j.dnarep.2011.10.004
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发表时间：
2012-01-02
期刊：
影响因子：
3.8
通讯作者：
Samson, Leona D.
中科院分区：
文献类型：
--
作者：
Fu, Dragony;Samson, Leona D.
外环乙烯基是一种高度突变的DNA损伤，与炎症和氯乙烯诱导的致癌密切相关。当烷基腺嘌呤脱氧核糖基酶(AAG或MPG)高亲和力地结合病变1，N6-乙烯腺嘌呤(εA)和3，N4-乙胞嘧啶(εC)时，只有εA可以被切除以启动碱基切除修复。在这里，我们发现人类ALKB同源2(ALKBH2)双加氧酶催化双链和单链εC损伤的直接逆转，其效率与经典的ALKBH2底物相当。值得注意的是，我们发现在体外，AAG与εC的非酶结合特异性地阻止了εC的催化修复，但不能阻止甲基化的AlkBH2底物的修复。这些结果确认人ALKBH2是突变εC损伤的修复酶，并强调了碱基切除和直接逆转DNA修复途径之间底物结合重叠的潜在后果。
Exocyclic ethenobases are highly mutagenic DNA lesions strongly implicated in inflammation and vinyl chloride-induced carcinogenesis. While the alkyladenine DNA glycosylase, AAG (or MPG), binds the etheno lesions 1,N6-ethenoadenine (εA) and 3,N4-ethenocytosine (εC) with high affinity, only εA can be excised to initiate base excision repair. Here, we discover that the human AlkB homolog 2 (ALKBH2) dioxygenase enzyme catalyzes direct reversal of εC lesions in both double- and single-stranded DNA with comparable efficiency to canonical ALKBH2 substrates. Notably, we find that in vitro, the non-enzymatic binding of AAG to εC specifically blocks ALKBH2-catalyzed repair of εC but not that of methylated ALKBH2 substrates. These results identify human ALKBH2 as a repair enzyme for mutagenic εC lesions and highlight potential consequences for substrate-binding overlap between the base excision and direct reversal DNA repair pathways.
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影响因子：
64.5
作者：
Rai K;Huggins IJ;James SR;Karpf AR;Jones DA;Cairns BR
通讯作者：
Cairns BR
影响因子：
2.9
作者：
Lee, Chun-Yue I.;Delaney, James C.;Kartalou, Maria;Lingaraju, Gondichatnahalli M.;Maor-Shoshani, Ayelet;Essigmann, John M.;Samson, Leona D.
通讯作者：
Samson, Leona D.
影响因子：
4.8
作者：
Abu, M;Waters, TR
通讯作者：
Waters, TR
影响因子：
7.4
作者：
MacCoss, MJ;Wu, CC;Yates, JR
通讯作者：
Yates, JR
DOI：
10.1073/pnas.94.24.12869
发表时间：
1997-11-25
影响因子：
11.1
作者：
Hang, B;Singer, B;Elder, RH
通讯作者：
Elder, RH