Cell Cycle Overview

Cell Cycle Overview

• The cell cycle is a series of events leading to cell duplication and division.
• In bacteria, cell growth and DNA replication happen throughout the cell cycle, with duplicated chromosomes distributed to daughter cells along the plasma membrane.
• Eukaryotic cell cycles are more complex, with DNA synthesis occurring in a specific phase.
• Replicated chromosomes are then distributed to daughter nuclei via complex events before cell division.
• The eukaryotic cell cycle consists of four coordinated processes: cell growth, DNA replication, chromosome distribution, and cell division.
• Eukaryotic cell cycles are divided into four discrete phases: M, G1, S, and G2.
• M phase involves mitosis, often followed by cytokinesis.
• The cell grows throughout interphase (G1, S, and G2).
• A typical human cell in culture divides approximately every 24 hours.
• Mitosis and cytokinesis take about one hour, with interphase comprising 95% of the cell cycle.
• The duration of cell cycle phases varies in different cell types.
• Budding yeasts, for instance, can complete the cycle in 90 minutes.
• Early embryonic cells have very short cycles, focusing on rapid cell division rather than growth.
• Some adult cells, like nerve cells, cease division altogether.
• Other cells divide occasionally to replace lost cells due to injury or death (e.g., skin fibroblasts, liver cells).
• These cells enter a quiescent stage called G0.

Regulation of Cell Cycle

• Cell cycle progression is regulated by external signals from the environment and internal signals that monitor and coordinate processes.
• The availability of growth factors typically controls animal cell cycles.
• Restriction point: If growth factors are unavailable during a specific part of G1, the cell enters G0.
• Cell cycle checkpoints control mechanisms ensuring proper cell cycle progression.
• Checkpoints detect damage (from external agents or DNA replication issues). This triggers a DNA damage response.
• Checkpoints also monitor chromosome attachment to the spindle.
• Several checkpoints function throughout the cell cycle for proper genome transmission to daughter cells.
• The coordination between cell cycle phases involves checkpoints that prevent entry into a subsequent phase until the preceding phase's events are completed.
• G1/S, Intra S, G2/M, and Spindle Assembly Checkpoints are noteworthy cellular checkpoints.
• Progression through checkpoints is dependent on cyclin-dependent kinases (CDKs) activated by cyclins. These protein subunits are produced at different stages to regulate specific events of the cell cycle.
• MCM proteins bind to origin recognition complex (ORC) proteins to restrict DNA replication to once per cell cycle. MCM proteins are only bound to DNA in G1, allowing replication initiation in S phase; they are displaced after initial replication, preventing further replication before mitosis.
• Protein kinases and cell cycle regulation are controlled by the families of Cyclins and Cyclin-dependent kinases (CDKs).
• Growth factors and DNA damage checkpoints contribute to G1 Cdk's regulation.
• p53 is a relevant tumor suppressor protein, also known as the guardian of the cell cycle.

The Events of M Phase

• M phase involves distinct phases of mitosis: Prophase, Prometaphase, Metaphase, Anaphase, and Telophase.
• Cdk1/Cyclin B controls progression to metaphase by inducing nuclear and cytoplasmic changes.
• The spindle assembly checkpoint ensures all chromosomes are aligned on the metaphase spindle before initiating anaphase.
• Spindle assembly checkpoint (SAC) is monitored for alignment of chromosomes on the metaphase spindle; if unaligned, the cell remains in metaphase.
• Metaphase to anaphase transition involves APC (anaphase-promoting complex) activation, which ubiquitinates regulatory proteins (like Securin), leading to sister chromatid separation and anaphase initiation.
• Cohesins bind to DNA during S phase to connect sister chromatids. They are replaced by condensins during M phase, which drives chromatin condensation.
• Breakdown of the nuclear envelope involves Cdk1/cyclin B phosphorylation of nuclear lamins, dissolving the filaments and releasing individual lamin dimers.