Poly (ADP‐ribose) polymerase inhibits DNA replication by human replicative DNA polymerase α, δ and ε in vitro

FEBS Letters

Eki, Toshihiko¹ 

[1]Division of Human Genome Research and Gene Bank, Tsukuba Life Science Center, The Institute of Physical and Chemical Research (RIKEN), 3-1-1 Koyadai, Tsukuba Science City, Ibaraki 305, Japan

关键词: Poly ADP-ribose polymerase;    Poly ADP-ribosylation;    Eukaryotic DNA replication;    Human DNA polymerase α;    δ and ε;    PARP;    poly (ADP-ribose) polymerase;    HSSB;    human single-stranded DNA binding protein (identical to replication protein A;    RP-A);    SV40;    simian virus 40;    T antigen;    virus-encoded large tumor antigen;    PCNA;    proliferating cell nuclear antigen;    A1;    activator 1 protein (identical to replication factor C;    RF-C);    DNA pol;    DNA polymerase;    BSA;    bovine serum albumin;    PMSF;    phenylmethylsulfonylfluoride;    DTT;    dithiothreitol;    kDa;    kilodalton;    kb;    kilo base;    nt;    nucleotide;   

DOI  :  10.1016/0014-5793(94)01280-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The influence of poly (ADP-ribose) polymerase (PARP) and poly ADP-ribosylation on DNA synthesis supported by human replicative DNA polymerase (DNA pol) α, δ, and ε has been examined using the replication system containing poly(dA)₄₅₀₀-oligo(dT)_12–18 as the template primer. PARP alone inhibited the pol activities in a dose-dependent manner even in the presence of the accessory factors for DNA pol δ, proliferating cell nuclear antigen (PCNA) and activator 1 (A1; RF-C). Both DNA pol α and ε activities were decreased approximately 10-fold under the poly ADP-ribosylating condition. In contrast, DNA synthesis by DNA pol δ holoenzyme was not affected by poly ADP-ribosylation like prokaryotic DNA pol's. The analysis of poly(dT) formed by DNA pol α and ε indicated that poly ADP-ribosylation mainly reduced the frequency of replication. These observations suggest a possibility that PARP acts as a negative regulator for the initiation of DNA replication upon cellular DNA damage.

【 授权许可】

Unknown