RAD18-BRCTx interaction is required for efficient repair of UV-induced DNA damage.

RAD18-BRCTx interaction is required for efficient repair of UV-induced DNA damage.
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RAD18-BRCTx 相互作用是有效修复紫外线诱导的 DNA 损伤所必需的。

DOI:
10.1016/j.dnarep.2011.10.012
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发表时间:
2012-02-01
期刊:
影响因子:
3.8
通讯作者:
Huang, Jun
Huang, Jun
中科院分区:
医学3区
文献类型:
--
作者:
Liu, Ting;Chen, Hongxia;Kim, Hongtai;Huen, Michael S. Y.;Chen, Junjie;Huang, Jun

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BRCA1羧基末端(BRCT)基序存在于许多参与DNA修复和/或DNA损伤信号通路的蛋白质中。BRCT结构域蛋白BRCTx已被证明与RAD18物理上相互作用,RAD18是一种参与复制后修复和同源重组修复的E3连接酶。然而,RAD18和BRCTx之间相互作用的生理学相关性在很大程度上尚不清楚。在这项研究中,我们证明了RAD18与BRCTx以一种依赖于磷酸化的方式相互作用,这种相互作用是BRCTx在DNA损伤部位积累所必需的,这种相互作用是通过RAD18 C末端高度保守的丝氨酸残基介导的。此外,我们发现了RAD18-BRCTx模块在紫外线诱导的DNA损伤修复中的关键作用,但不是增殖细胞核抗原的单一泛素化或同源重组。因此,我们的结果表明,RAD18在监测紫外线诱导的DNA损伤反应信号中具有额外的功能。
BRCA1 carboxyl-terminal (BRCT) motifs are present in a number of proteins involved in DNA repair and/or DNA damage signaling pathways. The BRCT domain-containing protein BRCTx has been shown to interact physically with RAD18, an E3 ligase involved in postreplication repair and homologous recombination repair. However, the physiological relevance of the interaction between RAD18 and BRCTx is largely unknown. In this study, we showed that RAD18 interacts with BRCTx in a phosphorylation-dependent manner and that this interaction, mediated via highly conserved serine residues on the RAD18 C terminus, is required for BRCTx accumulation at DNA damage sites. Furthermore, we uncovered critical roles of the RAD18-BRCTx module in UV-induced DNA damage repair but not PCNA mono-ubiquitination or homologous recombination. Thus, our results suggest that RAD18 has an additional function in the surveillance of the UV-induced DNA damage response signal.
DOI: 10.1016/j.dnarep.2009.04.004
发表时间: 2009-09-02
期刊: DNA repair
影响因子: 3.8
作者:
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通讯作者: Yaffe MB
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