Analysis for regulation of RNR activity during DNA damage repair

平衡的脱氧核糖核苷酸(DNTP)供应对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RRM1和RRM2在损伤部位积累得非常快。RRM1物理上绑定到Tip60。用I-SCEI盒对细胞进行染色质免疫沉淀分析表明，RRM1以Tip60依赖的方式结合到损伤部位。缺乏Tip60结合的活性RRM1突变体未能挽救RRM1缺失的G1期细胞受损的DNA修复。RRM1 C-末端片段抑制RNR募集使细胞对DNA损伤敏感。我们认为，依赖于Tip60的RNR募集在dNTP供应DNA修复中起着重要作用。

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.