Gilbert D M, Neilson A, Miyazawa H, DePamphilis M L, Burhans W C
Roche Institute of Molecular Biology, Roche Research Center, Nutley, New Jersey 07110, USA.
J Biol Chem. 1995 Apr 21;270(16):9597-606. doi: 10.1074/jbc.270.16.9597.
Mimosine has been reported to specifically prevent initiation of DNA replication in the chromosomes of mammalian nuclei. To test this hypothesis, the effects of mimosine were examined in several DNA replication systems and compared with the effects of aphidicolin, a specific inhibitor of replicative DNA polymerases. Our results demonstrated that mimosine inhibits DNA synthesis in mitochondrial, nuclear, and simian virus 40 (SV40) genomes to a similar extent. Furthermore, mimosine and aphidicolin were indistinguishable in their ability to arrest SV40 replication forks and mammalian nuclear chromosomal replication forks. In contrast to aphidicolin, mimosine did not inhibit DNA replication in lysates of mammalian cells supplied with exogenous deoxyribonucleotide triphosphate precursors for DNA synthesis. Mimosine also had no effect on initiation or elongation of DNA replication in Xenopus eggs or egg extracts containing high levels of deoxyribonucleotide triphosphates. In parallel with its inhibitory effect on DNA synthesis in mammalian cells, mimosine altered deoxyribonucleotide triphosphate pools in a manner similar to that reported for another DNA replication inhibitor that affects deoxyribonucleotide metabolism, hydroxyurea. Taken together, these results show that mimosine inhibits DNA synthesis at the level of elongation of nascent chains by altering deoxyribonucleotide metabolism.
据报道，含羞草素能特异性地阻止哺乳动物细胞核染色体中DNA复制的起始。为了验证这一假设，我们在几个DNA复制系统中检测了含羞草素的作用，并与复制性DNA聚合酶的特异性抑制剂阿非迪霉素的作用进行了比较。我们的结果表明，含羞草素对线粒体、细胞核和猿猴病毒40（SV40）基因组中的DNA合成具有相似程度的抑制作用。此外，在阻止SV40复制叉和哺乳动物核染色体复制叉方面，含羞草素和阿非迪霉素的能力没有差异。与阿非迪霉素不同，在为DNA合成提供外源脱氧核糖核苷三磷酸前体的哺乳动物细胞裂解物中，含羞草素并不抑制DNA复制。在含有高水平脱氧核糖核苷三磷酸的非洲爪蟾卵或卵提取物中，含羞草素对DNA复制的起始或延伸也没有影响。与它对哺乳动物细胞中DNA合成的抑制作用相一致，含羞草素以一种类似于另一种影响脱氧核糖核苷代谢的DNA复制抑制剂羟基脲的方式改变了脱氧核糖核苷三磷酸库。综上所述，这些结果表明，含羞草素通过改变脱氧核糖核苷代谢，在新生链延伸水平上抑制DNA合成。
