Excision of 8-oxoguanine within clustered damage by the yeast OGG1 protein
Excision of 8-oxoguanine within clustered damage by the yeast OGG1 protein
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DOI：
10.1093/nar/29.5.1107
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发表时间：
2001-03-01
影响因子：
14.9
通讯作者：
O'Neill, P
中科院分区：
文献类型：
--
作者：
David-Cordonnier, MH;Boiteux, S;O'Neill, P
电离辐射和拟辐射抗癌剂在DNA中形成放射性损伤，并且被认为是生物学上严重的。7，8-二氢-8-氧代鸟嘌呤（8-oxoG）是由氧化攻击引起的主要DNA损伤，如果先前未被真核生物中的OGG 1 DNA糖基化酶/AP裂解酶蛋白切除，则具有高度致突变性，导致高水平的G .C->T .A颠换。然而，8-oxoG在成簇的DNA损伤中可能对细胞的修复机制提出挑战。当另一种类型的损伤[二氢胸腺嘧啶、尿嘧啶、8-oxoG、脱碱基（AP）位点或各种类型的单链断裂（SSB）1]存在于与8-oxoG相对的互补链1、3或5个碱基5'或3'上时，确定酵母OGG 1切除8-oxoG的能力。碱基损伤对酵母OGG 1（yOGG 1）切除8-oxoG的影响很小或没有影响，而AP位点具有强烈的抑制作用。使用在缺口周围具有3 '-和5'-磷酸末端的寡核苷酸或通过用内切核酸酶III或人AP内切核酸酶1转化AP位点获得的各种类型的SSB强烈抑制yOGG 1切除8-oxoG。因此，AP位点或SSB的这种大的抑制作用可以最小化在簇状损伤内的8-oxoG加工中形成双链断裂的可能性。
Clustered damages are formed in DNA by ionising radiation and radiomimetic anticancer agents and are thought to be biologically severe. 7,8-dihydro-8-oxoguanine (8-oxoG), a major DNA damage resulting from oxidative attack, is highly mutagenic leading to a high level of G .C-->T .A transversions if not previously excised by OGG1 DNA glycosylase/AP lyase proteins in eukaryotes. However, 8-oxoG within clustered DNA damage may present a challenge to the repair machinery of the cell. The ability of yeast OGG1 to excise 8-oxoG was determined when another type of damage [dihydrothymine, uracil, 8-oxoG, abasic (AP) site or various types of single-strand breaks (SSBs)l] is present on the complementary strand 1, 3 or 5 bases 5' or 3' opposite to 8-oxoG. Base damages have little or no influence on the excision of 8-oxoG by yeast OGG1 (yOGG1) whereas an AP site has a strong inhibitory effect, Various types of SSBs, obtained using either oligonucleotides with 3'- and 5'-phosphate termini around a gap or through conversion of an AP site with either endonuclease III or human AP endonuclease 1, strongly inhibit excision of 8-oxoG by yOGG1. Therefore, this large inhibitory effect of an AP site or a SSB may minimise the probability of formation of a double-strand break in the processing of 8-oxoG within clustered damages.