Eukaryotic Cell Cycle Overview

Cell Cycle Overview

• Eukaryotic cells have a cell cycle divided into interphase and the mitotic (M) phase.
• Interphase is where the cell grows and copies its DNA.
• The mitotic (M) phase is where the cell separates its DNA into two sets and divides its cytoplasm, forming two new cells.

Eukaryotic Cell Cycle Stages

• G1 phase (Gap 1): The period before DNA replication.
• S phase (Synthesis): DNA replication occurs.
• G2 phase (Gap 2): Occurs before mitosis (M).
• G0 phase: Cells that have stopped dividing, like mature T lymphocytes, are out of the cell cycle. Quiescent cells can re-enter the G1 phase to resume division.

DNA Synthesis in S Phase

• DNA synthesis only occurs once per cell cycle and only during the S phase.
• Eukaryotic cells have control mechanisms for this, gene products governing transitions between phases.
• Cyclins are proteins changing in concentration at specific times. This cycle aspect gives them their name.
• Cyclin-dependent kinases (Cdks) are important proteins for regulating progression through the cell cycle.
• During S phase, nuclear DNA is completely replicated once. Chromatin is marked to prevent further replication until mitosis.
• Replication licensing is a process that ensures DNA is replicated only once per cycle.

Cell Cycle Checkpoints

• Cell cycle is controlled by checkpoints ensuring each phase completes correctly before the next.
• Key protein classes involved include cyclins and cyclin-dependent kinases (Cdks).
• G1 checkpoint: Checks for cell size, nutrients, growth factors, and DNA damage.
• S checkpoint: Checks for DNA synthesis being complete.
• G2 checkpoint: Checks for cell size, DNA replication, and damage.
• M checkpoint: Checks for chromosome spindle attachment.

CDK Enzymes and Checkpoints

• Kinases are a group of enzymes that move the cell to the next phase of the cell cycle.
• Kinases bind to cyclins to form a CDK complex.
• This complex phosphorylates a checkpoint protein that activates the protein and allows the cell cycle to continue.
• Checkpoint proteins are broken down after their role is done.
• Example: The D cyclins activate CDK4 and CDK6. These kinases are synthesized during G1 in actively dividing cells.

Retinoblastoma (Rb) Protein

• Rb is a substrate for CDK4 or CDK6.
• Rb binds to and inactivates a transcription factor (E2F).
• Phosphorylation of Rb by CDK4/6 releases E2F, activating gene transcription, and progression to S phase.

Cyclins and Their Corresponding Kinases

• Specific cyclins (D, E, A, B) regulate cell cycle progression by combining with specific kinases (CDK4/6, CDK2, CDK1) to drive the cycle.
• These complexes have specific tasks at particular points in the cell cycle (i.e., entry into S phase).

Cell Cycle and Cancer

• Cancer develops if cell cycle checkpoints are damaged, leading to uncontrolled cell division.
• Oncoviruses and oncogenes can disrupt normal cell cycle regulation.
• Excessive cyclin production, loss of CDK inhibitor, or a cyclin/CDK activation at the wrong time can cause uncontrolled cell division.
• Some cancer drugs are inhibitors for CDK complexes.

p53 and DNA Damage

• p53 activates transcription of genes that inhibit the cell cycle.
• p21 is a protein that efficiently inhibits the action of CDKs, which stops the cell cycle.
• If DNA damage is too extensive to repair, p53 triggers apoptosis.
• Cells lacking functional p53 are more susceptible to developing cancer. This is because p53 acts as a tumor suppressor.

DNA, Chromosome, Chromosome Segregation

• DNA, chromosome, and chromosome segregation integrity is monitored constantly in the cell cycle.
• If DNA damage, incomplete DNA replication or defective chromosome segregation machinery is detected, the cell cycle stops in the phase where defects exist.
• In some cases, irreparable damage can lead to programmed cell death (apoptosis).

This quiz covers the key components of the eukaryotic cell cycle, including interphase and the mitotic phase. You'll explore the stages of the cell cycle, including G1, S, G2, and G0 phases, as well as the mechanisms of DNA synthesis. Test your knowledge on cyclins and control mechanisms governing cell division.