Dynamic targeting of the replication machinery to sites of DNA damage.

Dynamic targeting of the replication machinery to sites of DNA damage.
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DOI:
10.1083/jcb.200312048
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发表时间:
2004-08-16
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Knudsen ES
Knudsen ES
中科院分区:
其他
文献类型:
--
作者:
Solomon DA;Cardoso MC;Knudsen ES

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DNA复制机制的组成部分定位于DNA损伤后的离散亚核灶,在那里它们在修复过程中发挥必要的功能。在这里,我们发现复制因子增殖细胞核抗原(PCNA)和RPAp 34在这些修复灶处以离散的动力学动态交换,并且这种行为与DNA复制期间的动力学不同。翻译后修饰被假设为针对特定的蛋白质进行修复,我们发现PCNA在损伤部位的积累和稳定需要monoubiquitination。与RPAp34的NH 2末端磷酸化指导蛋白修复的流行观点相反,我们证明了DNA依赖性蛋白激酶的磷酸化增强了RPAp34在修复病灶的营业额。总之,这些发现支持了一个动态交换模型,在该模型中,由特定修饰调控的多种修复因子可以进入DNA损伤位点并迅速翻转。
Components of the DNA replication machinery localize into discrete subnuclear foci after DNA damage, where they play requisite functions in repair processes. Here, we find that the replication factors proliferating cell nuclear antigen (PCNA) and RPAp34 dynamically exchange at these repair foci with discrete kinetics, and this behavior is distinct from kinetics during DNA replication. Posttranslational modification is hypothesized to target specific proteins for repair, and we find that accumulation and stability of PCNA at sites of damage requires monoubiquitination. Contrary to the popular notion that phosphorylation on the NH2 terminus of RPAp34 directs the protein for repair, we demonstrate that phosphorylation by DNA-dependent protein kinase enhances RPAp34 turnover at repair foci. Together, these findings support a dynamic exchange model in which multiple repair factors regulated by specific modifications have access to and rapidly turn over at sites of DNA damage.
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影响因子: --
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