PARP3 is a sensor of nicked nucleosomes and monoribosylates histone H2B(Glu2).
PARP3 is a sensor of nicked nucleosomes and monoribosylates histone H2B(Glu2).
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DOI：
10.1038/ncomms12404
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发表时间：
2016-08-17
影响因子：
16.6
通讯作者：
Caldecott KW
中科院分区：
文献类型：
--
作者：
Grundy GJ;Polo LM;Zeng Z;Rulten SL;Hoch NC;Paomephan P;Xu Y;Sweet SM;Thorne AW;Oliver AW;Matthews SJ;Pearl LH;Caldecott KW
PARP 3是ADP-核糖基转移酶超家族的一员，我们发现它加速了禽类DT 40细胞中染色体DNA单链断裂的修复。二维核磁共振实验表明，PARP 3采用保守的DNA结合界面来检测和稳定地结合DNA断裂，并在染色体损伤位点积累。PARP 3优先结合到含有带切口DNA的单核体并被其激活，所述单核体将PARP 3反式核糖基化活性靶向到单个组蛋白底物。尽管裸DNA中的切口刺激PARP 3自核糖基化，但单核体中的切口促进组蛋白H2 B特异性地在Glu 2处的反式核糖基化。这些数据将PARP 3鉴定为有切口核小体的分子传感器，并首次证明了染色质在位点特异性DNA单链断裂处的核糖基化。 染色体单链DNA断裂经常发生，需要修复以避免疾病后果。在这里，作者表明，在鸟类细胞中，PARP 3加速了这种修复，并使用结构生物学和细胞生物学技术来揭示作用机制的细节。
PARP3 is a member of the ADP-ribosyl transferase superfamily that we show accelerates the repair of chromosomal DNA single-strand breaks in avian DT40 cells. Two-dimensional nuclear magnetic resonance experiments reveal that PARP3 employs a conserved DNA-binding interface to detect and stably bind DNA breaks and to accumulate at sites of chromosome damage. PARP3 preferentially binds to and is activated by mononucleosomes containing nicked DNA and which target PARP3 trans-ribosylation activity to a single-histone substrate. Although nicks in naked DNA stimulate PARP3 autoribosylation, nicks in mononucleosomes promote the trans-ribosylation of histone H2B specifically at Glu2. These data identify PARP3 as a molecular sensor of nicked nucleosomes and demonstrate, for the first time, the ribosylation of chromatin at a site-specific DNA single-strand break. Chromosomal single-strand DNA breaks occur frequently and require repair to avoid disease outcomes. Here, the authors show that in bird cells, PARP3 accelerates this repair, and use structural biology and cell biology techniques to reveal details of the mechanism of action.