From yeast to mammals: the magical process of gene activation during S phase!

The management of the cell cycle is crucial in every aspect of life, especially in the S phase (synthesis phase), where DNA replication is central to the continued reproduction of organisms. When cells transition from G1 to S phase, the process must be both precise and rapid, as accurate gene replication is necessary for successful cell division. The control mechanism for cells entering the S phase not only exists in yeast, but has also been confirmed in mammalian cells, which has deepened our understanding of cell biology.

"The S phase is a critical node in the cell cycle, when cells must be fully prepared to achieve accurate gene replication."

Regulatory mechanism

The onset of the S phase is controlled by the G1 restriction point, which determines whether the cell enters the subsequent cell cycle. When the cell environment is suitable, cell growth signals promote the accumulation of Cln3 cyclin, causing it to form a complex with the cell cycle-dependent kinase CDK2. This complex can inhibit the transcriptional repressor Whi5, thereby promoting the expression of S phase genes.

"This process creates a positive feedback loop that ultimately reinforces the cell's commitment to S-phase gene expression."

DNA replication process

During the S phase, the cell's pre-replication complex (pre-RC) is converted into an active replication fork, initiating DNA replication. This process depends on the kinase activity of several S phase CDKs such as Cdc7, and cells must initiate this process accurately and orderly. During this process, the activation of many repeat origins is controlled, allowing DNA replication to flexibly adjust its speed in response to changes in the environment.

Histone Synthesis

In order to allow the newly synthesized DNA to be packaged into nucleosomes smoothly, basic (non-variant) histones are synthesized synchronously during the S phase. Early on, the cyclin E-Cdk2 complex phosphorylates NPAT, which promotes the transcription of histone genes, thereby accelerating the coordination of histone production and DNA synthesis.

"During the S phase, the accumulation of SLBP and the action of NPAT greatly improve the efficiency of histone production."

Nucleosome replication

During the process of DNA replication, new nucleosomes are formed. The study showed that this process does not rely entirely on a semi-conservative model, but rather proceeds in a conservative manner. This nucleosome duplication ensures that old and new histones are properly distributed into newly formed cells.

Reconstruction of chromatin domains

After cell division, daughter chromosomes face the challenge of re-establishing functional chromatin domains. Inheritance of old histones is sufficient to support accurate reconstruction of large-scale chromatin domains. However, for small genes, inherited histones may not be sufficient to accurately transmit modifications. At this time, the introduction of secondary histone variants has become a new direction for the study of chromatin structure.

DNA Damage Checkpoint

During S phase, cells continually check the integrity of their genome. Once DNA damage is detected, cells initiate several key S-phase checkpoint pathways that prevent the cell from further progression through the cycle. These checkpoints not only detect double-strand breaks but also coordinate responses at different stages of the cell cycle to ensure genome stability.

"These checkpoint mechanisms are an important means for cells to protect themselves by ensuring that cells do not divide when DNA damage occurs."

With the continuous progress of biological science research, our understanding of the cell cycle will continue to deepen. From gene activation in yeast to the replication mechanism of mammalian cells, this series of processes demonstrates the mysteries of life that operate in precision and coordination in nature. Behind these complex rules, we can't help but ask, if these processes are abnormal, what impact will it have on the entire organism?

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