Cooperative cluster formation, DNA bending and base-flipping by O6-alkylguanine-DNA alkyltransferase.
Cooperative cluster formation, DNA bending and base-flipping by O6-alkylguanine-DNA alkyltransferase.
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DOI：
10.1093/nar/gks574
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发表时间：
2012-09-01
影响因子：
14.9
通讯作者：
Fried MG
中科院分区：
文献类型：
--
作者：
Tessmer I;Melikishvili M;Fried MG
O 6-烷基鸟嘌呤-DNA烷基转移酶（AGT）修复DNA中的致突变O 6-烷基鸟嘌呤和O 4-烷基胸腺嘧啶加合物，保护基因组，也有助于肿瘤对化疗烷化剂的抗性。AGT结合DNA合作，合作的相互作用可能是重要的病变搜索和修复。我们研究了形态的复合物长，未修饰的DNA，使用分析超离心和原子力显微镜。AGT形成≤11个蛋白质的簇。由McGhee-von Hippel模型预测的更长的簇，即使在高[蛋白质]下也没有看到。有趣的是，由于DNA解旋的扭转应力有可能限制集群大小的观察范围。聚簇位点的DNA显示弯曲角（10 °、10 ° 30 °和10 ° 60°），这与每个蛋白诱导10 ° 30°弯曲的模型一致。复合物沿着DNA的分布与序列特异性不相容，但表明对DNA末端的适度偏好。这些特性告诉我们AGT可能发挥作用的环境。小的合作集群和适应一系列DNA弯曲的能力允许在DNA拓扑结构受到限制的情况下发挥作用，例如在DNA复制复合物附近。低序列特异性允许在整个基因组中进行有效和无偏的病变搜索。
O6-Alkylguanine-DNA alkyltransferase (AGT) repairs mutagenic O6-alkylguanine and O4-alkylthymine adducts in DNA, protecting the genome and also contributing to the resistance of tumors to chemotherapeutic alkylating agents. AGT binds DNA cooperatively, and cooperative interactions are likely to be important in lesion search and repair. We examined morphologies of complexes on long, unmodified DNAs, using analytical ultracentrifugation and atomic force microscopy. AGT formed clusters of ≤11 proteins. Longer clusters, predicted by the McGhee–von Hippel model, were not seen even at high [protein]. Interestingly, torsional stress due to DNA unwinding has the potential to limit cluster size to the observed range. DNA at cluster sites showed bend angles (∼0, ∼30 and ∼60°) that are consistent with models in which each protein induces a bend of ∼30°. Distributions of complexes along the DNA are incompatible with sequence specificity but suggest modest preference for DNA ends. These properties tell us about environments in which AGT may function. Small cooperative clusters and the ability to accommodate a range of DNA bends allow function where DNA topology is constrained, such as near DNA-replication complexes. The low sequence specificity allows efficient and unbiased lesion search across the entire genome.
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影响因子：
16.8
作者：
Daniels, DS;Woo, TT;Tainer, JA
通讯作者：
Tainer, JA
DOI：
10.1080/07391102.2010.10508585
发表时间：
2010-06-01
影响因子：
4.4
作者：
Arya, Gaurav;Maitra, Arijit;Grigoryev, Sergei A.
通讯作者：
Grigoryev, Sergei A.
影响因子：
2.9
作者：
LEROY, JL;CHARRETIER, E;GUERON, M
通讯作者：
GUERON, M
影响因子：
2.9
作者：
KOWALCZYKOWSKI, SC;PAUL, LS;VONHIPPEL, PH
通讯作者：
VONHIPPEL, PH
影响因子：
14.9
作者：
Bender, K;Federwisch, M;Rajewsky, MF
通讯作者：
Rajewsky, MF