Chapter 12: Mitosis and the Regulation of the Cell Cycle

Chapter 12: Mitosis

The Structure of the Duplicated Chromosome – Chromatids

The replication and distribution of large amounts of DNA are possible because DNA is packaged into structures called chromosomes. Each chromosome contains one extremely long DNA molecule associated with many proteins.

• Chromatin: The complex of DNA and proteins that makes up chromosomes.

• Genes: Units of heredity made up of DNA.

• Before cell division, chromosomes are duplicated, resulting in two sister chromatids joined at a region called the centromere.

• Sister chromatids contain identical DNA molecules.

• Once separated, each chromatid is considered an individual chromosome.

• Each sister chromatid contains a centromere, a specialized region of repetitive DNA where they are most tightly connected.

Example: A duplicated chromosome consists of two sister chromatids joined at the centromere. When the chromatids separate during mitosis, each becomes an independent chromosome.

The Cell Cycle and Its Regulation

All cells have a cell life cycle, starting as a cell that produces a duplicate of itself. The information from each cell is transmitted in a high-fidelity way to daughter cells.

• Cell Cycle: The ordered sequence of events in the life of a cell, from its origin to its division into two daughter cells.

• Phases: G1 (first gap), S (synthesis), G2 (second gap), and M (mitotic phase).

• Most of the time, cells are in the G1 phase, performing specific functions.

• Some cells, such as stem cells, can divide many times, while others are specialized and do not divide after maturity.

• Purpose of cell division: Growth, repair, reproduction, and development.

Example: Human stem cells can form various types of cells, while most adult cells are specialized and do not divide.

Goal of Mitotic Division

The main goal of mitosis is to ensure that each daughter cell receives an identical set of chromosomes. This process is essential for growth, repair, and asexual reproduction in eukaryotes.

• Ensures the maintenance of chromosome number across generations.

• Allows for the replacement of old or damaged cells.

• Supports the development of multicellular organisms from a single fertilized egg.

Role of Spindle Fibers in the Mitotic Process

Spindle fibers are essential for the movement and segregation of chromosomes during mitosis.

• Mitotic spindle: Forms in the cytoplasm during prophase, composed of microtubules and associated proteins.

• Spindle microtubules assemble by adding tubulin subunits.

• In animal cells, spindle fiber assembly begins at the centrosome.

• During metaphase, chromosomes align at the metaphase plate, and spindle fibers attach to kinetochores.

• During anaphase, spindle fibers shorten, pulling sister chromatids apart toward opposite poles.

Example: The "tug-of-war" effect created by spindle fibers ensures accurate chromosome segregation.

The Role of Kinases and Cyclin in the Regulation of the Cell Life Cycle Through Checkpoints

The cell cycle is regulated by a set of molecules that trigger and coordinate key events. The main regulators are protein kinases and cyclins.

• Checkpoints: Control points where stop and go-ahead signals regulate the cycle.

• Cyclin-dependent kinases (Cdks): Enzymes that are active only when bound to cyclin proteins.

• MPF (Maturation Promoting Factor): A cyclin-Cdk complex that triggers a cell's passage past the G2 checkpoint into mitosis.

• Regulation ensures that cells do not divide before they are ready.

Example: If cyclin is degraded, MPF activity drops, and the cell cannot proceed to mitosis.

Density-Dependent Inhibition and Growth Factors

Cell division is also regulated by external signals such as growth factors and cell density.

• Growth factors: Proteins released by certain cells that stimulate other cells to divide.

• Density-dependent inhibition: Crowded cells stop dividing.

• Anchorage dependence: Cells must be attached to a substrate to divide.

Example: Most animal cells will not divide unless they are attached to a surface, such as the extracellular matrix.

Relationship Between Cell Life Cycle and Cancer

Cancer cells do not respond to normal cell cycle controls. They divide uncontrollably and can invade other tissues.

• Cancer cells may not exhibit density-dependent inhibition or anchorage dependence.

• They may produce their own growth factors or have abnormal signaling pathways.

• The underlying cause is usually a mutation in genes that regulate the cell cycle.

• Cancer cells can divide indefinitely in culture if supplied with nutrients (immortal).

• Abnormal cell behavior can lead to tumor formation and metastasis.

Example: HeLa cells are a famous example of immortal cancer cells used in research.

Concept Check: Impact of a Nonfunctional CAK Gene

If the CAK gene was nonfunctional, MPF would not become fully active. The cell would be stuck in the cell cycle, unable to enter mitosis, resulting in disrupted cell division and cell cycle regulation.