Lesson 4

Cell cycle and checkpoints

This lesson explores the intricate stages of the cell cycle, from interphase to mitosis, and the crucial regulatory checkpoints that ensure proper cell division. Understanding these processes is fundamental to comprehending growth, development, and the mechanisms underlying diseases like cancer.

Learning Objectives

By the end of this lesson, you will be able to:

Describe the distinct phases of the cell cycle, including interphase (G1, S, G2) and M phase (mitosis/meiosis and cytokinesis).
Explain the roles of cell cycle checkpoints (G1, G2, M) in regulating cell division.
Identify the key regulatory molecules, such as cyclins and cyclin-dependent kinases (CDKs), that control cell cycle progression.
Analyze the consequences of unregulated cell division and the failure of cell cycle checkpoints.

Key Concepts

Cell Cycle

Definition: The ordered sequence of events that a cell passes through from the time it is formed until it divides into two daughter cells. It consists of interphase (cell growth and DNA replication) and the mitotic (M) phase (cell division).

Example: A skin cell undergoing repeated cycles of division to replace old or damaged cells demonstrates the cell cycle in action.

Cell Cycle Checkpoints

Definition: Control mechanisms in the eukaryotic cell cycle that ensure proper progression through the different phases, preventing errors such as DNA damage or incorrect chromosome segregation. These checkpoints monitor internal and external conditions and can halt the cycle until conditions are favorable or problems are corrected.

Example: The G1 checkpoint ensures that the cell has sufficient resources and undamaged DNA before committing to DNA replication.

Cyclins and CDKs

Definition: Cyclins are a family of proteins that activate cyclin-dependent kinases (CDKs). CDKs are enzymes that, once activated by cyclins, phosphorylate target proteins to drive the cell through different stages of the cell cycle. The concentration of cyclins fluctuates throughout the cell cycle, while CDK concentrations remain relatively constant.

Example: Mitotic cyclins bind to and activate mitotic CDKs, triggering the events that lead to the cell entering mitosis.

Apoptosis

Definition: Programmed cell death, a highly regulated process where a cell self-destructs in a controlled manner. It is essential for development, tissue homeostasis, and eliminating damaged or unwanted cells, especially those that fail cell cycle checkpoints.

Example: The removal of webbing between fingers and toes during embryonic development is an example of apoptosis.

Lesson Content

Phases of the Cell Cycle

The cell cycle is broadly divided into two main phases: Interphase and the Mitotic (M) phase. Interphase, the longest phase, involves cell growth and DNA replication, preparing the cell for division. The M phase encompasses both nuclear division (mitosis or meiosis) and cytoplasmic division (cytokinesis).

Interphase consists of G1 (first gap/growth), S (DNA synthesis), and G2 (second gap/growth) phases.
During the S phase, the cell's DNA is replicated, resulting in two identical sister chromatids.
The M phase includes mitosis (prophase, metaphase, anaphase, telophase) and cytokinesis, leading to two daughter cells.

Regulation by Cyclins and Cyclin-Dependent Kinases (CDKs)

The progression through the cell cycle is tightly regulated by a complex system of proteins, primarily cyclins and cyclin-dependent kinases (CDKs). CDKs are enzymes that are only active when bound to specific cyclins. The fluctuating concentrations of different cyclins throughout the cell cycle determine which CDKs are active at specific times, thereby driving the cell from one phase to the next.

Cyclins bind to and activate CDKs, forming cyclin-CDK complexes.
Active cyclin-CDK complexes phosphorylate target proteins, initiating specific cell cycle events.
Different cyclins (e.g., G1 cyclins, S cyclins, M cyclins) are synthesized and degraded at specific points in the cycle.

Cell Cycle Checkpoints

Critical checkpoints exist at various stages of the cell cycle to ensure that cell division occurs accurately and only when conditions are appropriate. These checkpoints act as surveillance mechanisms, monitoring DNA integrity, chromosome behavior, and cell size/resources. If issues are detected, the cell cycle can be temporarily halted or, in severe cases, trigger apoptosis.

The G1 checkpoint (restriction point) checks for cell size, nutrients, growth factors, and DNA damage.
The G2 checkpoint ensures DNA replication is complete and DNA is undamaged before entering mitosis.
The M checkpoint (spindle assembly checkpoint) verifies that all sister chromatids are correctly attached to the spindle microtubules before anaphase.

Consequences of Checkpoint Failure

Failure of cell cycle checkpoints can lead to uncontrolled cell proliferation and genomic instability, which are hallmarks of cancer. When damaged cells bypass these crucial regulatory points, mutations can accumulate, and abnormal cells can continue to divide, potentially forming tumors. Understanding these mechanisms is vital for cancer research and therapy.

Uncontrolled cell division due to checkpoint failure is a primary characteristic of cancer.
Mutations in genes encoding checkpoint regulators (e.g., tumor suppressor genes like p53) can lead to cancer.
Apoptosis is a vital mechanism to eliminate cells that fail to pass checkpoints, preventing the propagation of errors.

AP Exam Tips

Be able to identify and describe the events occurring in each phase of interphase and mitosis, and clearly distinguish between them.
Understand the roles of cyclins and CDKs as a regulatory system; focus on their interaction and how their activity changes throughout the cell cycle.
Memorize the locations and specific functions of the three main checkpoints (G1, G2, M) and what they monitor. Connect checkpoint failure to diseases like cancer.

Summary

The cell cycle, comprising interphase and M phase, is a precisely regulated process ensuring accurate cell division. Key checkpoints, controlled by cyclin-CDK complexes, monitor cellular conditions and DNA integrity, preventing errors. Disruptions in this regulation can lead to uncontrolled cell growth and diseases such as cancer.

Bài học tiếp theo

Cancer overview