Translocation of human ribosomal protein S3 to sites of DNA damage is dependant on ERK-mediated phosphorylation following genotoxic stress
Translocation of human ribosomal protein S3 to sites of DNA damage is dependant on ERK-mediated phosphorylation following genotoxic stress
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DOI：
10.1016/j.dnarep.2007.04.009
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发表时间：
2007-10-01
期刊：
影响因子：
3.8
通讯作者：
Deutsch, Walter A.
中科院分区：
文献类型：
--
作者：
Yadavilli, Sridevi;Hede, Vijay;Deutsch, Walter A.
除了在翻译和核糖体成熟中的作用之外，人核糖体蛋白S3（hS 3）还参与DNA损伤识别，如通过其在体外对DNA中的脱碱基位点和7，8-二氢-8-氧代鸟嘌呤（8-oxoG）残基的亲和力所反映的。在这里，我们表明，hS 3是能够进行这两个角色，其离体易位从细胞质到细胞核的遗传毒性应激的结果。hS 3的转位依赖于ERK 1/2介导的hS 3的苏氨酸残基（T42）的磷酸化。两个不同的异位表达的T42定点突变体未能响应条件下的遗传毒性应激，从而提供了一个链接之间的DNA损伤和ERK 1/2依赖磷酸化的hS 3。最后，在暴露的细胞中追踪hS 3与8-oxoG灶的共定位，提高了hS 3是细胞DNA损伤反应途径的成员的可能性，该途径导致其与DNA损伤位点的相互作用。(C)2007 Elsevier B. V.保留所有权利。
Besides its role in translation and ribosome maturation, human ribosomal protein S3 (hS3) is implicated in DNA damage recognition as reflected by its affinity for abasic sites and 7,8-dihydro-8-oxoguanine (8-oxoG) residues in DNA in vitro. Here, we demonstrate that hS3 is capable of carrying out both roles by its ex vivo translocation from the cytoplasm to the nucleus as a consequence of genotoxic stress. The translocation of hS3 is dependent on ERK1/2-mediated phosphorylation of a threonine residue (T42) of hS3. Two different ectopically expressed site-directed mutants of T42 failed to respond to conditions of genotoxic stress, thus providing a link between DNA damage and ERK1/2 dependent phosphorylation of hS3. Lastly, hS3 was traced in exposed cells to its co-localization with 8-oxoG foci, raising the possibility that hS3 is a member of a cellular DNA damage response pathway that results in its interaction with sites of DNA damage. (C) 2007 Elsevier B.V. All rights reserved.