CK2 phosphorylation-dependent interaction between aprataxin and MDC1 in the DNA damage response.
CK2 phosphorylation-dependent interaction between aprataxin and MDC1 in the DNA damage response.
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DOI：
10.1093/nar/gkp1149
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发表时间：
2010-03
影响因子：
14.9
通讯作者：
Lavin MF
中科院分区：
文献类型：
--
作者：
Becherel OJ;Jakob B;Cherry AL;Gueven N;Fusser M;Kijas AW;Peng C;Katyal S;McKinnon PJ;Chen J;Epe B;Smerdon SJ;Taucher-Scholz G;Lavin MF
Aprataxin在1型神经退行性疾病共济失调动眼运动性失用症中存在缺陷，可以在DNA修复过程中解决流产的DNA连接中间产物。在这里，我们证明了aprataxin定位于高LET辐射诱导的DNA损伤部位，并通过磷酸化依赖的相互作用与DNA损伤检查点蛋白1(MDC1/NFBD1)的介体结合。这种相互作用是通过MDC1APRATAIN FHA结构域和多个酪蛋白激酶2二磷酸化的S-D-T-D基序介导的。对aprataxin FHA结构域的X射线结构和突变分析，结合对pSDpTD肽相互作用的模拟，表明了一种不寻常的FHA结合机制，该结合机制是由规范的PT-对接位点及其周围的一簇碱性残基介导的。Aprataxin FHA Arg29突变阻止了其与mdc1的相互作用，并阻止了其在DNA损伤部位的募集。这些结果表明，aprataxin不仅参与单链断裂的修复，而且可能通过与MDC1的相互作用参与处理双链断裂的子集。
Aprataxin, defective in the neurodegenerative disorder ataxia oculomotor apraxia type 1, resolves abortive DNA ligation intermediates during DNA repair. Here, we demonstrate that aprataxin localizes at sites of DNA damage induced by high LET radiation and binds to mediator of DNA-damage checkpoint protein 1 (MDC1/NFBD1) through a phosphorylation-dependent interaction. This interaction is mediated via the aprataxin FHA domain and multiple casein kinase 2 di-phosphorylated S-D-T-D motifs in MDC1. X-ray structural and mutagenic analysis of aprataxin FHA domain, combined with modelling of the pSDpTD peptide interaction suggest an unusual FHA binding mechanism mediated by a cluster of basic residues at and around the canonical pT-docking site. Mutation of aprataxin FHA Arg29 prevented its interaction with MDC1 and recruitment to sites of DNA damage. These results indicate that aprataxin is involved not only in single strand break repair but also in the processing of a subset of double strand breaks presumably through its interaction with MDC1.
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DOI：
10.1083/jcb.200510130
发表时间：
2006-04-24
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bekker-Jensen S;Lukas C;Kitagawa R;Melander F;Kastan MB;Bartek J;Lukas J
通讯作者：
Lukas J
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
3.4
作者：
Jakob, B.;Splinter, J.;Taucher-Scholz, G.
通讯作者：
Taucher-Scholz, G.
影响因子：
30.8
作者：
Date, H;Onodera, O;Tsuji, S
通讯作者：
Tsuji, S
影响因子：
4.8
作者：
Coster, Gideon;Hayouka, Zvi;Goldberg, Michal
通讯作者：
Goldberg, Michal