Sheinin R, Setterfield G, Dardick I, Kiss G, Dubsky M
Can J Biochem. 1980 Dec;58(12):1359-69. doi: 10.1139/o80-185.
Mouse L-cells treated with cytosine arabinoside, hydroxyurea, fluorodeoxyuridine, methotrexate, or mitomycin C rapidly cease DNA synthesis and stop dividing. Such inhibition of DNA replication is followed by interruption of formation of lysine- and arginine-containing proteins, including chromatin-bound histones, and by a major reorganization of the heterochromatin of the central nucleoplasm, manifest as disaggregation of large clumps of this condensed chromatin. Morphometric analysis revealed both cell and nuclear enlargement in cells treated with such antimetabolites of DNA replication. These observations are in contrast to those made with WT-4 cells starved of isoleucine or treated with cycloheximide. Isoleucine depletion was associated with inhibition of DNA synthesis and continued increase of cell and nuclear volume, but not with massive disaggregation of heterochromatin. Cycloheximide produced inhibition of DNA synthesis and protoplasmic growth, and also prevented structural reorganization of chromatin. A model is presented which suggests that initiation of chromatin replication is associated with a process, dependent upon de novo protein synthesis, which results in chromatin disaggregation. This can be revealed by inhibition of the correct replication of chromatin DNA and chromatin protein.
用阿糖胞苷、羟基脲、氟脱氧尿苷、甲氨蝶呤或丝裂霉素C处理的小鼠L细胞会迅速停止DNA合成并停止分裂。这种对DNA复制的抑制之后，会导致含赖氨酸和精氨酸的蛋白质（包括与染色质结合的组蛋白）的形成中断，以及核中央核质的异染色质发生重大重组，表现为这种浓缩染色质的大团块解聚。形态计量分析显示，用这种DNA复制抗代谢物处理的细胞中，细胞和细胞核均增大。这些观察结果与用缺乏异亮氨酸的WT - 4细胞或用环己酰亚胺处理的细胞的观察结果形成对比。异亮氨酸缺乏与DNA合成抑制以及细胞和细胞核体积持续增加有关，但与异染色质的大量解聚无关。环己酰亚胺会抑制DNA合成和原生质生长，还会阻止染色质的结构重组。本文提出了一个模型，该模型表明染色质复制的起始与一个依赖于从头合成蛋白质的过程相关，这个过程会导致染色质解聚。这可以通过抑制染色质DNA和染色质蛋白质的正确复制来揭示。
