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Mechanism for differential sensitivity of the chromosome and growth cycles of mammalian cells to the rate of protein synthesis.

机译:哺乳动物细胞的染色体和生长周期对蛋白质合成速率的差异敏感性的机制。

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It has been documented widely that when the generation times of eucaryotic cells are lengthened by slowing the rate of protein synthesis, the duration of the chromosome cycle (S, G2, and M phases) remains relatively invariant. Paradoxically, when the growth of exponentially growing cultures of CHO cells is partially inhibited with inhibitors of protein synthesis, the immediate effect is a proportionate reduction in the rate of total protein, histone protein, and DNA synthesis. However, on further investigation it was found that over the next 2 h the rates of histone protein and DNA synthesis recover, in some cases completely to the uninhibited rate, while the synthesis rates of other proteins do not recover. We called this process chromosome cycle compensation. The amount of compensation seen in CHO cell cultures can account quantitatively for the relative invariance in the length of the chromosome cycle (S, G2, and M phases) reported for these cells. The mechanism for this compensation involves a specific increase in the levels of histone mRNAs. An invariant chromosome cycle coupled with a lengthening growth cycle must result in a disproportionate lengthening of the G1 phase. Thus, these results suggest that chromosome cycle invariance may be due more to specific cellular compensation mechanisms rather than to the more usual interpretation involving a rate-limiting step for cell cycle progression in the G1 phase.
机译:已有广泛文献记载,当通过减慢蛋白质合成速度来延长真核细胞的生成时间时,染色体周期(S,G2和M期)的持续时间保持相对不变。矛盾的是,当蛋白质合成抑制剂部分抑制CHO细胞的指数生长时,其直接作用是总蛋白质,组蛋白和DNA合成速率的相应降低。但是,在进一步研究中发现,在接下来的2小时内,组蛋白和DNA合成的速率得以恢复,在某些情况下完全恢复为未抑制的速率,而其他蛋白质的合成速率则没有恢复。我们称此过程为染色体周期补偿。在CHO细胞培养物中看到的补偿量可以定量解释这些细胞报道的染色体周期(S,G2和M期)长度的相对不变性。这种补偿的机制涉及组蛋白mRNA水平的特定增加。不变的染色体周期加上延长的生长周期必须导致G1期的不成比例的延长。因此,这些结果表明染色体周期不变性可能更多是由于特定的细胞补偿机制所致,而不是由于更常见的解释,即涉及G1期细胞周期进程的限速步骤。

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