在 G1 期 DNA 修复过程中，Tip60 依赖性的核苷酸还原酶在 DNA 损伤部位的募集对于 DNA 修复至关重要。

Essential role of Tip60-dependent recruitment of ribonucleotide reductase at DNA damage sites in DNA repair during G1 phase.

机构信息

Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University Medical School, Nagoya 467-8601, Japan.

出版信息

Genes Dev. 2010 Feb 15;24(4):333-8. doi: 10.1101/gad.1863810.

DOI:10.1101/gad.1863810

PMID:20159953

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2816732/

Abstract

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.

摘要

核苷酸（dNTP）的平衡供应对于 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 RRM1 和 RRM2 会迅速在损伤部位积累。RRM1 与 Tip60 物理结合。用 I-SceI 盒进行细胞染色质免疫沉淀分析显示，RRM1 以 Tip60 依赖的方式结合到损伤部位。缺乏与 Tip60 结合的活性 RRM1 突变体不能挽救 RRM1 耗尽的 G1 期细胞中受损的 DNA 修复。RRM1 C 端片段抑制 RNR 的募集可使细胞对 DNA 损伤敏感。我们提出 Tip60 依赖性 RNR 募集在 DNA 修复的 dNTP 供应中起着重要作用。