Essential role of Tip60-dependent recruitment of ribonucleotide reductase at DNA damage sites in DNA repair during G1 phase
Essential role of Tip60-dependent recruitment of ribonucleotide reductase at DNA damage sites in DNA repair during G1 phase
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DOI：
10.1101/gad.1863810
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发表时间：
2010-02-15
影响因子：
10.5
通讯作者：
Nakanishi, Makoto
中科院分区：
文献类型：
--
作者：
Niida, Hiroyuki;Katsuno, Yuko;Nakanishi, Makoto
平衡的脱氧核糖核苷酸（dNTP）供应对于DNA修复至关重要。在这里，我们发现核糖核苷酸还原酶（RNR）亚基RRM 1和RRM 2在损伤部位非常迅速地积累。RRM 1与Tip 60物理结合。染色质免疫沉淀分析的细胞与I-SceI盒显示，RRM 1绑定到一个损伤位点的Tip 60依赖性的方式。缺乏Tip 60结合的活性RRM 1突变体未能挽救RRM 1耗尽的G1期细胞中受损的DNA修复。RRM 1 C-末端片段抑制RNR募集使细胞对DNA损伤敏感。我们认为，Tip 60依赖的RNR募集在DNA修复的dNTP供应中起着至关重要的作用。
A balanced deoxyribonucleotide (dNTP) supply is essential for DNA repair. Here, we found that ribonucleotide reductase (RNR) subunits RRM1 and RRM2 accumulated very rapidly at damage sites. RRM1 bound physically to Tip60. Chromatin immunoprecipitation analyses of cells with an I-SceI cassette revealed that RRM1 bound to a damage site in a Tip60-dependent manner. Active RRM1 mutants lacking Tip60 binding failed to rescue an impaired DNA repair in RRM1-depleted G1-phase cells. Inhibition of RNR recruitment by an RRM1 C-terminal fragment sensitized cells to DNA damage. We propose that Tip60-dependent recruitment of RNR plays an essential role in dNTP supply for DNA repair.