The current model of replication-dependent (RD) histone biosynthesis posits that RD histone gene expression is coupled to DNA replication, occurring only in S phase of the cell cycle once DNA synthesis has begun. However, several key factors in the RD histone biosynthesis pathway are up-regulated by E2F or phosphorylated by CDK2, suggesting these processes may instead begin much earlier, at the point of cell-cycle commitment. In this study, we use both fixed- and live-cell imaging of human cells to address this question, revealing a hybrid model in which RD histone biosynthesis is first initiated in G1, followed by a strong increase in histone production in S phase of the cell cycle. This suggests a mechanism by which cells that have committed to the cell cycle build up an initial small pool of RD histones to be available for the start of DNA replication, before producing most of the necessary histones required in S phase. Thus, a clear distinction exists at completion of mitosis between cells that are born with the intention of proceeding through the cell cycle and replicating their DNA and cells that have chosen to exit the cell cycle and have no immediate need for histone synthesis.

目前的复制依赖性 (RD) 组蛋白生物合成模型假定 RD 组蛋白基因表达与 DNA 复制相关，一旦 DNA 合成开始，仅在细胞周期的 S 期发生。然而，RD 组蛋白生物合成途径中的几个关键因素被 E2F 上调或被 CDK2 磷酸化，这表明这些过程可能更早开始，在细胞周期承诺点。在这项研究中，我们使用人类细胞的固定细胞和活细胞成像来解决这个问题，揭示了一个混合模型，其中 RD 组蛋白生物合成首先在 G1 开始，然后在 S 期组蛋白产生强烈增加细胞周期。这表明了一种机制，在这种机制下，已经参与细胞周期的细胞在产生 S 期所需的大部分必要组蛋白之前，会建立一个初始的小 RD 组蛋白池，可用于开始 DNA 复制。因此，在有丝分裂完成时存在明显的区别，这些细胞出生时的目的是通过细胞周期并复制其 DNA 和选择退出细胞周期且不需要立即合成组蛋白的细胞。