PARP-2 and PARP-3 are selectively activated by 5' phosphorylated DNA breaks through an allosteric regulatory mechanism shared with PARP-1.
PARP-2 and PARP-3 are selectively activated by 5' phosphorylated DNA breaks through an allosteric regulatory mechanism shared with PARP-1.
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DOI：
10.1093/nar/gku474
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发表时间：
2014-07
影响因子：
14.9
通讯作者：
Pascal JM
中科院分区：
文献类型：
--
作者：
Langelier MF;Riccio AA;Pascal JM
PARP-1、PARP-2和PARP-3是DNA依赖性PARP，其定位于DNA损伤，合成共价连接至包括其自身的靶蛋白的聚（ADP-核糖）（PAR），从而将修复因子募集至DNA断裂以提高修复效率。PARP-1、PARP-2和PARP-3的C-末端共有两个结构域--Trp-Gly-Arg（WGR）和催化结构域（CAT）。相比之下，PARP-1的N-末端区（NTR）超过500个残基，包括4个调节结构域，而PARP-2和PARP-3具有较小的NTR（分别为70和40个残基），结构组成和功能未知。在这里，我们发现PARP-2和PARP-3优先被含有5′磷酸（5′P）的DNA断裂激活，这表明选择性激活响应于特定的DNA修复中间体，特别是能够进行DNA连接的结构。与PARP-1相反，PARP-2和PARP-3的NTR对于DNA结合或DNA依赖性活化不是严格需要的。相反，WGR结构域是PARP-2和PARP-3的中央调节结构域。最后，PARP-1，PARP-2和PARP-3共享的变构调节机制的DNA依赖的催化激活通过局部不稳定的CAT。总的来说，我们的研究提供了新的见解的专门化的DNA依赖的PARP和它们的特定作用在DNA修复途径。
PARP-1, PARP-2 and PARP-3 are DNA-dependent PARPs that localize to DNA damage, synthesize poly(ADP-ribose) (PAR) covalently attached to target proteins including themselves, and thereby recruit repair factors to DNA breaks to increase repair efficiency. PARP-1, PARP-2 and PARP-3 have in common two C-terminal domains—Trp-Gly-Arg (WGR) and catalytic (CAT). In contrast, the N-terminal region (NTR) of PARP-1 is over 500 residues and includes four regulatory domains, whereas PARP-2 and PARP-3 have smaller NTRs (70 and 40 residues, respectively) of unknown structural composition and function. Here, we show that PARP-2 and PARP-3 are preferentially activated by DNA breaks harboring a 5′ phosphate (5′P), suggesting selective activation in response to specific DNA repair intermediates, in particular structures that are competent for DNA ligation. In contrast to PARP-1, the NTRs of PARP-2 and PARP-3 are not strictly required for DNA binding or for DNA-dependent activation. Rather, the WGR domain is the central regulatory domain of PARP-2 and PARP-3. Finally, PARP-1, PARP-2 and PARP-3 share an allosteric regulatory mechanism of DNA-dependent catalytic activation through a local destabilization of the CAT. Collectively, our study provides new insights into the specialization of the DNA-dependent PARPs and their specific roles in DNA repair pathways.
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通过PARP-1，需要通过PARP-1进行反馈调节的聚（ADP-核糖基），才能快速响应活细胞中的DNA损伤。
影响因子：
14.9
作者：
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作者：
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通讯作者：
Hottiger MO
影响因子：
14.9
作者：
Beck C;Boehler C;Guirouilh Barbat J;Bonnet ME;Illuzzi G;Ronde P;Gauthier LR;Magroun N;Rajendran A;Lopez BS;Scully R;Boussin FD;Schreiber V;Dantzer F
通讯作者：
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