NME3与Tip60在DNA修复中的直接相互作用。

The direct interaction of NME3 with Tip60 in DNA repair.

作者信息

Tsao Ning, Yang Ya-Chi, Deng Yu-Jyun, Chang Zee-Fen

机构信息

Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan (R.O.C.).

Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan (R.O.C.).

出版信息

Biochem J. 2016 May 1;473(9):1237-45. doi: 10.1042/BCJ20160122. Epub 2016 Mar 4.

DOI:10.1042/BCJ20160122

PMID:26945015

Abstract

Cellular supply of dNTPs via RNR (ribonucleotide reductase) is crucial for DNA replication and repair. It has been shown that DNA-damage-site-specific recruitment of RNR is critical for DNA repair efficiency in quiescent cells. The catalytic function of RNR produces dNDPs. The subsequent step of dNTP formation requires the function of NDP kinase. There are ten isoforms of NDP kinase in human cells. In the present study, we identified NME3 as one specific NDP kinase that interacts directly with Tip60, a histone acetyltransferase, to form a complex with RNR. Our data reveal that NME3 recruitment to DNA damage sites depends on this interaction. Disruption of interaction of NME3 with Tip60 suppressed DNA repair in serum-deprived cells. Thus Tip60 interacts with RNR and NME3 to provide site-specific synthesis of dNTP for facilitating DNA repair in serum-deprived cells which contain low levels of dNTPs.

摘要

通过核糖核苷酸还原酶（RNR）进行的脱氧核苷三磷酸（dNTP）的细胞供应对于DNA复制和修复至关重要。研究表明，RNR在DNA损伤位点的特异性募集对于静止细胞中的DNA修复效率至关重要。RNR的催化功能产生脱氧核苷二磷酸（dNDP）。dNTP形成的后续步骤需要核苷二磷酸激酶的功能。人类细胞中有十种核苷二磷酸激酶同工型。在本研究中，我们鉴定出NME3是一种特定的核苷二磷酸激酶，它直接与组蛋白乙酰转移酶Tip60相互作用，与RNR形成复合物。我们的数据表明，NME3募集到DNA损伤位点取决于这种相互作用。NME3与Tip60相互作用的破坏抑制了血清饥饿细胞中的DNA修复。因此，Tip60与RNR和NME3相互作用，提供dNTP的位点特异性合成，以促进血清饥饿细胞（其中dNTP水平较低）中的DNA修复。