11/15 CELL CYCLE

Upcoming Assignments and Exam Dates

• DMP Analysis: Due Sunday

• Perusal Assignments:

  • Topic: Cell Signaling and Cancer, Due Sunday Night

  • Topic: Apoptosis and p53, Due Tuesday Night

• Exam: 6th Exam on November 25th

• Thanksgiving Break: Last week of November; classes on Monday and Tuesday

• Last Week of Classes: 1st week of December

• Final Exam Week: 2nd week of December

Overview of Cell Cycle Regulation

• The cell cycle regulation involves understanding the timing and conditions for each phase.

• Major checkpoints include:

  • G1 to S checkpoint

  • G2 to M checkpoint

  • Metaphase to Anaphase checkpoint

Cell Cycle Stages

• Mitosis: Process where cells divide into two daughter cells.

• Focus on the phases of the cell cycle:

  • Interphase: Cell growth and DNA replication.

    • Comprises G1 (growth), S (DNA synthesis), and G2 (preparation for mitosis).

  • M Phase: Mitosis and cytokinesis.

Checkpoints in the Cell Cycle

G1 to S Checkpoint

• Checks for:

  • Growth factors: Signals for the cell to divide.

  • Nutrients: Availability essential for DNA replication.

  • Cell size: Ensures cells are large enough for division.

  • DNA damage: Ensures genetic integrity before replication.

G2 to M Checkpoint

• Focuses on:

  • Cell size: Verifying growth post-DNA replication.

  • DNA damage assessment: Ensuring no errors before mitosis.

  • Completion of DNA replication: Confirms all chromosomes are duplicated.

Metaphase to Anaphase Checkpoint

• Essential for:

  • Proper alignment of chromosomes at the metaphase plate.

  • Ensuring each sister chromatid is attached to spindle fibers from opposite poles.

Molecules Involved in Cell Cycle Regulation

• Cyclins: Proteins whose concentration changes throughout the cycle, activating CDKs.

• Cyclin-Dependent Kinases (CDKs): Enzymes that phosphorylate target proteins to drive cell cycle events:

  • CDK Activity Regulation: Inactive without binding to cyclins.

  • Types of Cyclins:

    • S Cyclin: Binds to CDKs to initiate S phase.

    • M Cyclin: Binds to CDKs to initiate M phase.

Mechanism of Cyclin/CDK Action

• When a cyclin binds to a CDK, a conformational change activates the kinase for phosphorylation of target proteins.

• Role of phosphorylation:

  • Activates proteins that promote cell division.

  • Phosphorylation can also deactivate proteins at other points.

• Cyclin Degradation: Occurs post-mitotic phase by proteasome to prevent CDK activity, allowing the cell to exit M phase.

Anaphase Promoting Complex (APC)

• Functions during the metaphase to anaphase transition:

  • Ubiquitinates cyclins for degradation, signaling the end of mitosis.

  • Activates Separase by degrading Securin, allowing cohesin degradation, which liberates sister chromatids for separation.

Summary of Checkpoint Functions

• The G1 to S checkpoint ensures favorable conditions for DNA replication.

• The G2 to M checkpoint checks for growth and completion of DNA replication.

• The Metaphase to Anaphase checkpoint guarantees equal distribution of chromosomes.

• The regulatory roles of cyclins and CDKs underscore the complexity of the cell cycle, highlighting the importance of protein interactions in cellular functions.

Upcoming Assignments and Exam Dates

• DMP Analysis: Due Sunday. This assignment focuses on Data Management Protocols, requiring a thorough analysis of theoretical and practical implications in data handling.

• Perusal Assignments:

  • Topic: Cell Signaling and Cancer: Due Sunday Night. This assignment investigates the mechanisms by which signaling pathways contribute to cancer progression, emphasizing protein interactions and genetic changes.

  • Topic: Apoptosis and p53: Due Tuesday Night. This assignment covers the role of the p53 protein in regulating apoptosis, its significance in tumor suppression, and its interactions with cellular stress responses.

• Exam: 6th Exam on November 25th. This exam will cover all material discussed up to this point, with a focus on cell cycle regulation, signaling pathways, and mechanisms of disease.

• Thanksgiving Break: Last week of November; classes will resume on Monday and Tuesday.

• Last Week of Classes: 1st week of December.

• Final Exam Week: 2nd week of December.

Overview of Cell Cycle Regulation

The regulation of the cell cycle is critical for ensuring proper cellular function and division. It involves a intricate series of checkpoints that monitor the timing and conditions necessary for each phase of the cycle, allowing for the maintenance of genomic integrity and proper cell function.

Major Checkpoints

1. G1 to S Checkpoint: Verifies that the cell is ready for DNA synthesis, monitoring factors like growth signals and DNA integrity.

2. G2 to M Checkpoint: Ensures readiness for mitosis by confirming that DNA replication is complete and without damage.

3. Metaphase to Anaphase Checkpoint: Checks the alignment of chromosomes to ensure an equal distribution during cell division.

Cell Cycle Stages

• Mitosis: A process where a single cell divides to form two genetically identical daughter cells, critical for growth, development, and repair.

• Interphase: Where the majority of the cell's life occurs, encompassing:

  • G1 Phase: Cellular growth where the cell increases its size and synthesizes proteins required for DNA synthesis.

  • S Phase: The synthesis phase where DNA is replicated to ensure that each daughter cell will have an identical set of chromosomes.

  • G2 Phase: A second growth phase where the cell prepares for mitosis by producing necessary proteins and organelles.

• M Phase: The phase of mitosis and cytokinesis, where the cell actually divides.

Checkpoints in the Cell Cycle

G1 to S Checkpoint

• Checks for:

  • Growth Factors: Signals required for promoting cell division.

  • Nutrients: Ensures availability of essential materials for DNA replication.

  • Cell Size: Verifies that the cell is of adequate size to divide.

  • DNA Damage: Checks for any damage to DNA to maintain genetic integrity.

G2 to M Checkpoint

• Focuses on:

  • Cell Size: Validates that growth has occurred post-DNA synthesis.

  • DNA Damage Assessment: Ensures there are no errors in the DNA.

  • Completion of DNA Replication: Confirms all chromosomes are duplicated before proceeding to mitosis.

Metaphase to Anaphase Checkpoint

• Essential for:

  • Validating proper alignment and attachment of chromosomes at the metaphase plate.

  • Ensuring each sister chromatid is firmly attached to spindle fibers originating from opposite poles, which is vital for accurate chromosome segregation.

Molecules Involved in Cell Cycle Regulation

• Cyclins: Regulatory proteins that vary in concentration throughout the cell cycle, crucial for the activation of Cyclin-Dependent Kinases (CDKs).

• Cyclin-Dependent Kinases (CDKs): Enzymes that phosphorylate target proteins to trigger specific events in the cell cycle. CDKs are inactive without cyclin binding.

  • Types of Cyclins:

    • S Cyclin: Activates CDKs necessary for transitioning into the S phase and initiating DNA replication.

    • M Cyclin: Activates CDKs that trigger the onset of mitosis.

Mechanism of Cyclin/CDK Action

When a cyclin binds to a CDK, it induces a conformational change that activates the kinase function. This activation leads to the phosphorylation of various target proteins, promoting advancement through the cell cycle. Phosphorylation plays a dual role: not only activating proteins that encourage cell cycle progression but also deactivating proteins at other stages to prevent untimely division. The degradation of cyclins post-mitosis, primarily through proteasomal pathways, is crucial to halt CDK activity, thereby allowing the cell to exit M phase safely.

Anaphase Promoting Complex (APC)

• Functions during the critical transition from metaphase to anaphase by facilitating the degradation of cyclins through ubiquitin tagging. This process signals the conclusion of mitosis and is essential for the proper separation of sister chromatids.

• Role of Separase Activation: APC also activates Separase by degrading Securin, leading to the degradation of cohesin, which is necessary for the separation of sister chromatids at anaphase.

Summary of Checkpoint Functions

• The G1 to S checkpoint ensures that conditions are favorable and safe for DNA replication to commence, setting the stage for a successful cell cycle.

• The G2 to M checkpoint ascertains that growth has occurred as expected and that DNA replication has been completed without error.

• The Metaphase to Anaphase checkpoint secures that chromosome alignment is perfect, ensuring equal distribution during anaphase.

The complexities in cell cycle regulation, particularly through the interactions between cyclins and CDKs, highlight the critical nature of these molecular mechanisms in maintaining cellular health and preventing diseases such as cancer. Understanding these processes is fundamental for biology and medicine.