The involvement of ATP produced via (ADP-Ribose)n in the maintenance of DNA replication apparatus during DNA repair
The involvement of ATP produced via (ADP-Ribose)n in the maintenance of DNA replication apparatus during DNA repair
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DOI：
10.1248/bpb.30.447
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发表时间：
2007-03-01
影响因子：
2
通讯作者：
Tanuma, Sei-ichi
中科院分区：
文献类型：
--
作者：
Maruta, Hidehara;Okita, Naoyuki;Tanuma, Sei-ichi
已表明由聚（ADP-核糖）[（ADP-R）（n）]产生的ATP的形成是修复受损DNA所必需的。在这里，我们调查这种ATP是否参与DNA修复过程中的DNA复制过程。从同步化的HeLa S3细胞中分离出聚ADP核糖基化的S期中期细胞核，然后用DNA损伤剂N-甲基-N '-硝基-N-亚硝基胍（MNNG）处理，发现在加入3 mM ATP开始DNA合成之前，仅在焦磷酸盐（PPi）存在下预孵育去聚ADP核糖基化期间，聚ADP核糖基化的S期中期细胞核保留DNA复制合成活性。在与PPi预孵育期间，在存在聚（ADP-核糖）糖水解酶（PARG）的有效和特异性抑制剂Oenothein B（Oen B）的情况下，该DNA复制活性不被维持。在PPi预孵育过程中，（ADP-R）（n）产生了μ m数量级的ATP。这些结果表明，（ADP-R）（n）产生的ATP在DNA修复过程中对维持复制装置具有重要作用。
The formation of ATP produced from poly(ADP-ribose) [(ADP-R)(n)] has been suggested to be required to repair damaged DNA. Here we investigate whether this ATP is involved in DNA replication processes during DNA repair. Poly(ADP-ribosylated mid-S phase cell nuclei, which were isolated from synchronized HeLa S3 cells followed by the treatment with a DNA damaging agent, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), were revealed to retain DNA replication synthesizing activity during preincubation for de-poly(ADP-ribosyl)ation only in the presence of pyrophosphate (PPi) before DNA synthesis was started by adding 3 mm ATP. This DNA replication activity was not maintained in the presence of a potent and specific inhibitor of poly(ADP-ribose) glycohydrolase (PARG), Oenothein B (Oen B ) during the preincubation with PPi. In the preincubation with PPi, mu m orders of ATP was produced from (ADP-R)(n), These results point to an important function of ATP generated from (ADP-R)(n) in nuclei for the maintenance of replication apparatus during DNA repair.