The role of ADP-ribosylation in regulating DNA interstrand crosslink repair.
The role of ADP-ribosylation in regulating DNA interstrand crosslink repair.
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DOI：
10.1242/jcs.193375
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发表时间：
2016-10-15
影响因子：
4
通讯作者：
Lakin ND
中科院分区：
文献类型：
--
作者：
Gunn AR;Banos-Pinero B;Paschke P;Sanchez-Pulido L;Ariza A;Day J;Emrich M;Leys D;Ponting CP;Ahel I;Lakin ND
ADP-核糖基转移酶（ART）通过ADP-核糖相互作用结构域促进损伤位点修复因子的富集，从而在DNA链断裂修复中发挥作用。在这里，我们利用简单的真核生物Dictyosteoblasts发现ADP-核糖基化在调节DNA链间交联修复和冗余的非同源末端连接（NHEJ）这一途径的作用。计算机检索用于鉴定含有排列的宏结构域的蛋白质（我们称之为aprataxin/APLF-and-PNKP-like protein; APL）。结构分析表明，这个排列的宏域保留与ADP-核糖相互作用相关的功能，APL能够通过这个宏域结合聚（ADP-核糖）。APL在对顺铂治疗（一种诱导DNA链间交联（ICL）的药物）的反应中富含染色质。这取决于APL和ART Adprt 2的宏结构域，表明ADP-核糖基化在细胞对顺铂的反应中的作用。虽然adprt 2 −细胞对顺铂敏感，但由于双链断裂（DSB）响应性ART Adprt 1a的冗余信号，ADP核糖基化在这些细胞中很明显，促进了NHEJ介导的修复。这些数据暗示了DNA ICL修复中的ADP-核糖基化，并确定了NHEJ可以在不存在Adprt 2的情况下发挥作用以解决这种形式的DNA损伤。总结：在这里，我们确定了翻译后修饰ADP-核糖基化的作用，在响应DNA链间交联模型Dictyosteoprotein。
ADP-ribosylation by ADP-ribosyltransferases (ARTs) has a well-established role in DNA strand break repair by promoting enrichment of repair factors at damage sites through ADP-ribose interaction domains. Here, we exploit the simple eukaryote Dictyostelium to uncover a role for ADP-ribosylation in regulating DNA interstrand crosslink repair and redundancy of this pathway with non-homologous end-joining (NHEJ). In silico searches were used to identify a protein that contains a permutated macrodomain (which we call aprataxin/APLF-and-PNKP-like protein; APL). Structural analysis reveals that this permutated macrodomain retains features associated with ADP-ribose interactions and that APL is capable of binding poly(ADP-ribose) through this macrodomain. APL is enriched in chromatin in response to cisplatin treatment, an agent that induces DNA interstrand crosslinks (ICLs). This is dependent on the macrodomain of APL and the ART Adprt2, indicating a role for ADP-ribosylation in the cellular response to cisplatin. Although adprt2− cells are sensitive to cisplatin, ADP-ribosylation is evident in these cells owing to redundant signalling by the double-strand break (DSB)-responsive ART Adprt1a, promoting NHEJ-mediated repair. These data implicate ADP-ribosylation in DNA ICL repair and identify that NHEJ can function to resolve this form of DNA damage in the absence of Adprt2. Summary: Here, we identify a role for post-translational modification ADP-ribosylation in the response to DNA interstrand crosslinks in the model Dictyostelium.
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影响因子：
16
作者：
Ben-Yehoyada M;Wang LC;Kozekov ID;Rizzo CJ;Gottesman ME;Gautier J
通讯作者：
Gautier J
影响因子：
4
作者：
Couto, C. Anne-Marie;Hsu, Duen-Wei;Lakin, Nicholas D.
通讯作者：
Lakin, Nicholas D.
DOI：
10.1002/dvg.22867
发表时间：
2015-08
期刊：
Genesis (New York, N.Y. : 2000)
影响因子：
--
作者：
Basu S;Fey P;Jimenez-Morales D;Dodson RJ;Chisholm RL
通讯作者：
Chisholm RL
影响因子：
64.8
作者：
Ahel, Ivan;Ahel, Dragana;West, Stephen C.
通讯作者：
West, Stephen C.
影响因子：
14.9
作者：
CORPET, F
通讯作者：
CORPET, F