6月10日，Nature Structural & Molecular Biology杂志在线报道了聚腺苷酸二磷酸核糖转移酶-1(PARP1)识别DNA链断裂点的结构生物学机理研究最新进展。
聚腺苷酸二磷酸核糖转移酶-1(PARP1)是DNA损伤的主要感受器。其ADP核糖聚合酶活力由DNA断裂反应精确调节。在DNA损伤位点的活化下，PARP1通过共价添加长链和分支多聚ADP核糖，修饰其自身及其他蛋白。该修饰还可招募下游DNA修复和染色体重构因子。PARP1通过其N端DNA结合结构域（DBD）识别DNA损伤。DBD包含一个不同寻常的锌指（ZnF）串联重复结构域。
该研究确定了人类结合DNA断裂位点的PARP1-DBD的晶体结构。结合对PARP1招募到DNA损伤位点的体内功能研究，该晶体结构揭示了来源于不同PARP1分子的ZnF1和ZnF2结构域形成的二聚化装配复合物的结构。该复合结构构成一个断裂链识别单元，通过加速其二聚化和反式自我修饰，帮助激活PARP1。（生物谷bioon.com)
doi:10.1016/j.cell.2011.10.017
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The zinc-finger domains of PARP1 cooperate to recognize DNA strand breaks
Ammar A E Ali,1, 5 Gyula Timinszky,2, 3, 5 Raquel Arribas-Bosacoma,1 Marek Kozlowski,2, 3 Paul O Hassa,2, 4 Markus Hassler,2, 3 Andreas G Ladurner,2, 3 Laurence H Pearl1 & Antony W Oliver1
Poly(ADP-ribose) polymerase 1 (PARP1) is a primary DNA damage sensor whose (ADP-ribose) polymerase activity is acutely regulated by interaction with DNA breaks. Upon activation at sites of DNA damage, PARP1 modifies itself and other proteins by covalent addition of long, branched polymers of ADP-ribose, which in turn recruit downstream DNA repair and chromatin remodeling factors. PARP1 recognizes DNA damage through its N-terminal DNA-binding domain (DBD), which consists of a tandem repeat of an unusual zinc-finger (ZnF) domain. We have determined the crystal structure of the human PARP1-DBD bound to a DNA break. Along with functional analysis of PARP1 recruitment to sites of DNA damage in vivo, the structure reveals a dimeric assembly whereby ZnF1 and ZnF2 domains from separate PARP1 molecules form a strand-break recognition module that helps activate PARP1 by facilitating its dimerization and consequent trans-automodification.
