Decreased rates of replicon initiation in mammalian cells

Decreased rates of replicon initiation in mammalian cells
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DOI:
10.1111/j.1432-1033.1996.0489k.x
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发表时间:
1996-04-01
期刊:
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子:
--
通讯作者:
Russev, G
Russev, G
中科院分区:
其他
文献类型:
--
作者:
Tsvetkov, L;Russev, G

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我们设计了一种测定Friend红白血病细胞中DNA合成起始速率的试验,并表明该参数可通过γ-辐射和4 '-去甲基表鬼臼毒素-9-(4,6-O-亚乙基-β-D-吡喃葡萄糖苷)(VP-16)处理而降低。可以得出结论,DNA双链断裂是这种效应的直接原因。复制子起始速率的降低受到不同试剂如顺式二氨二氯铂(II)、放线菌酮、星形孢菌素和3-氨基苯甲酰胺的不同影响。对这些结果的分析表明,所观察到的DNA起始速率的部分降低最有可能通过一个或多个磷酸化/去磷酸化步骤从损伤位点传递到起始位点。它不需要从头合成蛋白质因子,但可能依赖于DNA断裂位点染色质的聚(ADP-核糖基)化。
We have designed an assay to measure the rate of initiation of DNA synthesis in Friend erythroleukemia cells and have shown that this parameter is reduced by gamma-radiation and treatment with 4'-demethylepipodophyllotoxin-9-(4,6-O-ethylene-beta-D-glucopyranoside) (VP-16). It is concluded, that double-strand breaks in DNA are the immediate cause for this effect. The decrease in the rate of replicon initiation is affected differently by different agents such as cis-diamminedichloroplatinum(II), cycloheximide, staurosporine, and 3-aminobenzamide. The analysis of these results indicates that the observed partial decrease of the rate of DNA initiation is most probably transmitted from the site of damage to the initiation site by one or more phosphorylation/dephosphorylation steps. It does not require de novo synthesis of protein factors, but is probably dependent on poly(ADP-ribosyl)ation of chromatin at the site of DNA breaks.