The FHA and BRCT domains recognize ADP-ribosylation during DNA damage response.
The FHA and BRCT domains recognize ADP-ribosylation during DNA damage response.
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DOI：
10.1101/gad.226357.113
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发表时间：
2013-08-15
影响因子：
10.5
通讯作者：
Yu X
中科院分区：
文献类型：
--
作者：
Li M;Lu LY;Yang CY;Wang S;Yu X
多聚ADP核糖基化翻译后修饰在许多生物学过程中起着重要作用，包括DNA损伤反应。Yu及其同事现在鉴定了一组识别聚（ADP-核糖）（PAR）的Forkhead相关（FHA）和BRCA 1 C-末端（BRCT）结构域。他们表明PAR和Nijmegan断裂综合征蛋白NBS 1的BRCT结构域之间的相互作用对于ATM响应DNA损伤的激活是重要的。因此，这项研究表明，两个新的PAR结合模块介导的DNA损伤反应。聚腺苷二磷酸核糖基化是一种独特的翻译后修饰，参与许多生物学过程，如DNA损伤反应。在这里，我们证明了一组叉头相关（FHA）和BRCA 1的C-末端（BRCT）域识别聚（ADP-核糖）（PAR）在体外和体内。在这些FHA和BRCT结构域中，APTX和PNKP的FHA结构域与异ADP-核糖（PAR的连接）相互作用，而Ligase 4、XRCC 1和NBS 1的BRCT结构域识别ADP-核糖（PAR的基本单位）。PAR与FHA或BRCT结构域之间的相互作用介导这些含有结构域的蛋白质重新定位到DNA损伤位点，并促进DNA损伤反应。此外，PAR和NBS 1 BRCT结构域之间的相互作用对于DNA损伤反应期间ATM的早期激活和ATM依赖性细胞周期检查点激活是重要的。总之，我们的研究结果表明，两个新的PAR结合模块，在DNA损伤反应中发挥重要作用。
Poly-ADP-ribosylation post-translational modifications play important roles in many biological processes, including the DNA damage response. Yu and colleagues now identify a set of Forkhead-associated (FHA) and BRCA1 C-terminal (BRCT) domains that recognize poly(ADP-ribose) (PAR). They show that the interaction between PAR and the BRCT domain of the Nijmegan breakage syndrome protein NBS1 is important for the activation of ATM in response to DNA damage. This study thus demonstrates how two novel PAR-binding modules mediate the DNA damage response. Poly-ADP-ribosylation is a unique post-translational modification participating in many biological processes, such as DNA damage response. Here, we demonstrate that a set of Forkhead-associated (FHA) and BRCA1 C-terminal (BRCT) domains recognizes poly(ADP-ribose) (PAR) both in vitro and in vivo. Among these FHA and BRCT domains, the FHA domains of APTX and PNKP interact with iso-ADP-ribose, the linkage of PAR, whereas the BRCT domains of Ligase4, XRCC1, and NBS1 recognize ADP-ribose, the basic unit of PAR. The interactions between PAR and the FHA or BRCT domains mediate the relocation of these domain-containing proteins to DNA damage sites and facilitate the DNA damage response. Moreover, the interaction between PAR and the NBS1 BRCT domain is important for the early activation of ATM during DNA damage response and ATM-dependent cell cycle checkpoint activation. Taken together, our results demonstrate two novel PAR-binding modules that play important roles in DNA damage response.
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