title: The direct interaction of NME3 with Tip60 in DNA repair.
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.
authors.affiliation: Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan (R.O.C.).
authors.forename: Ning
authors.initials: N
authors.lastname: Tsao
authors.affiliation: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan (R.O.C.).
authors.forename: Ya-Chi
authors.initials: YC
authors.lastname: Yang
authors.affiliation: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan (R.O.C.).
authors.forename: Yu-Jyun
authors.initials: YJ
authors.lastname: Deng
authors.affiliation: 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.) zfchang@ym.edu.tw.
authors.forename: Zee-Fen
authors.initials: ZF
authors.lastname: Chang
mesh_terms: D004260:DNA Repair / Q000502:physiology*; D006367:HeLa Cells; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000074443:Lysine Acetyltransferase 5; D061986:MCF-7 Cells; D054778:NM23 Nucleoside Diphosphate Kinases / Q000235:genetics / Q000378:metabolism*; D012264:Ribonucleotide Reductases / Q000235:genetics / Q000378:metabolism*
chemical_list: D054778:NM23 Nucleoside Diphosphate Kinases; D012264:Ribonucleotide Reductases; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5; C517942:NME3 protein, human
keywords: DNA repair; NME3; Tip60; ribonucleotide reductase