Evidence for the involvement of DNA repair enzyme NEIL1 in nucleotide excision repair of (5'R)- and (5'S)-8,5'-cyclo-2'-deoxyadenosines.
Evidence for the involvement of DNA repair enzyme NEIL1 in nucleotide excision repair of (5'R)- and (5'S)-8,5'-cyclo-2'-deoxyadenosines.
复制标题
DOI：
10.1021/bi902161f
复制
发表时间：
2010-02-16
期刊：
影响因子：
2.9
通讯作者：
Dizdaroglu, Miral
中科院分区：
文献类型：
--
作者：
Jaruga, Pawel;Xiao, Yan;Vartanian, Vladimir;Lloyd, R. Stephen;Dizdaroglu, Miral
DNA修复酶NEIL1是一种DNA糖基化酶，参与氧化诱导DNA损伤的碱基切除修复（BER）的第一步。NEIL1对4,6-二氨基-5-甲脒嘧啶（FapyAde）和2,6-二氨基-4-羟基-5-甲脒嘧啶（FapyGua）表现出强烈的选择性，而对8-羟基鸟嘌呤（8-OH-Gua）没有特异性。在这项研究中，我们报告了（5’r）-8,5’-环-2’-脱氧腺苷（R-cdA）和（5’s）-8,5’-环-2’-脱氧腺苷（S-cdA）在未暴露于外源性氧化应激的neil1−/−小鼠的肝脏DNA中显著积累，而对照组或ogg1−/−小鼠的肝脏DNA中未观察到这些病变的积累。neil1−/−和ogg1−/−小鼠的肝脏DNA中均检测到FapyGua的显著积累，而8-OH-Gua仅在ogg1−/−中积累。由于R-cdA和S-cdA在碱基和糖段之间含有一个8,5 '共价键，因此它们不能被BER修复。有证据表明，这些病变可通过核苷酸切除修复（NER）修复。由于neil1 - / -小鼠中R-cdA和S-cdA的积累强烈表明它们的修复失败，这些数据表明neil1参与了R-cdA和S-cdA的NER。进一步的研究旨在阐明NEIL1在NER中的作用机制。
The DNA repair enzyme NEIL1 is a DNA glycosylase that is involved in the first step of base excision repair (BER) of oxidatively induced DNA damage. NEIL1 exhibits a strong preference for excision of 4,6-diamino-5-formamidopyrimidine (FapyAde) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua) from DNA with no specificity for 8-hydroxyguanine (8-OH-Gua). In this study, we report on the significant accumulation of (5′R)-8,5′-cyclo-2′-deoxyadenosine (R-cdA) and (5′S)-8,5′-cyclo-2′-deoxyadenosine (S-cdA) in liver DNA of neil1−/− mice that were not exposed to exogenous oxidative stress, while no accumulation of these lesions was observed in liver DNA from control or ogg1−/− mice. Significant accumulation of FapyGua was detected in liver DNA of both neil1−/− and ogg1−/− mice, while 8-OH-Gua accumulated in ogg1−/− only. Since R-cdA and S-cdA contain an 8,5′-covalent bond between the base and sugar moieties, they cannot be repaired by BER. There is evidence that these lesions are repaired by nucleotide excision repair (NER). Since the accumulation of R-cdA and S-cdA in neil1−/− mice strongly points to the failure of their repair, these data suggest that NEIL1 is involved in NER of R-cdA and S-cdA. Further studies aimed at elucidating the mechanism of action of NEIL1 in NER are warranted.
登录
查看更多内容
影响因子：
3.8
作者：
Kirkali, Gueldal;de Souza-Pinto, Nadja C.;Dizdaroglu, Miral
通讯作者：
Dizdaroglu, Miral
影响因子：
14.9
作者：
Morland, I;Rolseth, V;Seeberg, E
通讯作者：
Seeberg, E
影响因子：
14.9
作者：
Dherin, C;Radicella, JP;Boiteux, S
通讯作者：
Boiteux, S
影响因子：
3.8
作者：
Chan MK;Ocampo-Hafalla MT;Vartanian V;Jaruga P;Kirkali G;Koenig KL;Brown S;Lloyd RS;Dizdaroglu M;Teebor GW
通讯作者：
Teebor GW
DOI：
10.1073/pnas.062053799
发表时间：
2002-03-19
影响因子：
11.1
作者：
Hazra, TK;Izumi, T;Mitra, S
通讯作者：
Mitra, S