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The Cell Cycle and Molecular Biology of Cancer: Study Notes

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Chapter 12: The Cell Cycle

Big Idea and Overview

The cell cycle is fundamental to understanding how organisms grow, reproduce, and maintain their tissues. Cell division is the process by which a single cell gives rise to two genetically identical daughter cells, ensuring continuity of life and accurate transmission of genetic material.

Key Roles of Cell Division

Functions of Cell Division

  • Asexual reproduction: Single-celled organisms reproduce by dividing into new organisms.

  • Growth and development: Multicellular organisms develop from a single cell through repeated cell divisions.

  • Tissue renewal and repair: Cell division replaces damaged or dead cells in multicellular organisms.

Asexual reproduction, growth and development, tissue renewal

Cellular Organization of Genetic Material

Genome, Chromosomes, and Chromatin

  • Genome: All the DNA in a cell; prokaryotes typically have a single DNA molecule, while eukaryotes have multiple.

  • Chromosomes: DNA molecules packaged with proteins; each carries hundreds to thousands of genes.

  • Chromatin: The complex of DNA and protein in eukaryotic chromosomes, which condenses during cell division.

  • Somatic cells: Nonreproductive cells with two sets of chromosomes.

  • Gametes: Reproductive cells (sperm and eggs) with half the chromosome number of somatic cells.

Eukaryotic chromatin structure

Distribution of Chromosomes During Eukaryotic Cell Division

Chromosome Replication and Separation

  • Before cell division, DNA is replicated and chromosomes condense.

  • Each duplicated chromosome consists of two sister chromatids, joined by cohesins at the centromere.

  • During cell division, sister chromatids separate and become individual chromosomes.

Duplicated chromosome with sister chromatids and centromeresHomologous chromosomes, replication, sister chromatids, centromereHomologous chromosomes and replication

Phases of the Cell Cycle

Interphase and M Phase

The cell cycle consists of interphase (cell growth and chromosome duplication) and the mitotic (M) phase (mitosis and cytokinesis).

  • Interphase: Divided into G1 (growth), S (DNA replication), and G2 (preparation for division).

  • Mitosis: Division of the nucleus, conventionally broken into five stages: prophase, prometaphase, metaphase, anaphase, and telophase.

  • Cytokinesis: Division of the cytoplasm, resulting in two daughter cells.

Interphase cell with centrioles, nucleus, chromatinParent cell division into two genetically identical daughter cells

Stages of Mitosis

Prophase, Prometaphase, Metaphase, Anaphase, Telophase

  • Prophase: Chromosomes condense, spindle apparatus forms, nuclear envelope breaks down.

  • Prometaphase: Microtubules attach to kinetochores, chromosomes begin moving to the cell center.

  • Metaphase: Chromosomes align at the metaphase plate.

  • Anaphase: Sister chromatids separate and move to opposite poles.

  • Telophase: Spindle disassembles, nuclear envelope reforms, chromosomes uncoil.

Stages of mitosis with spindle apparatus and chromosome movement

The Mitotic Spindle and Chromosome Movement

Spindle Apparatus and Kinetochore Function

  • Mitotic spindle: Structure made of microtubules that controls chromosome movement.

  • Centrosomes: Microtubule-organizing centers that replicate and migrate to opposite poles.

  • Kinetochore: Protein complex at the centromere where spindle microtubules attach.

  • Microtubules shorten by depolymerizing at kinetochore ends, moving chromosomes during anaphase.

Cytokinesis

Differences in Animals and Plants

  • Animal cells: Cytokinesis occurs by cleavage, forming a cleavage furrow.

  • Plant cells: Cytokinesis occurs by formation of a cell plate.

Binary Fission in Bacteria

Prokaryotic Cell Division

  • Bacteria reproduce by binary fission, where the chromosome replicates and the cell divides.

  • Binary fission is simpler than mitosis and may represent an evolutionary precursor to eukaryotic cell division.

Cell Cycle Regulation

Checkpoints, Cyclins, and Cdks

  • The cell cycle is regulated by checkpoints (G1, G2, M) that ensure proper division.

  • G1 = cell growing G2=chromosomes have been replicated/DNA not damaged M=sister chromatids are correctly attached to the spindle microtubules

  • Cyclins: Proteins with cyclically fluctuating concentrations.

  • Cyclin-dependent kinases (Cdks): Enzymes that must bind cyclins to be active; increased = division; rises and falls

  • MPF (Maturation-promoting factor): Cyclin-Cdk complex that triggers entry into M phase.

Cell cycle control system overview

Internal and External Signals

Cell Cycle Control Mechanisms

  • Internal signals ensure chromosomes are properly attached before anaphase.

  • External signals include growth factors, such as PDGF, which stimulate cell division.

Loss of Cell Cycle Controls in Cancer

Cancer Cell Characteristics

  • Cancer cells ignore normal cell cycle controls and continue dividing without growth factors.

  • Transformation allows cells to divide indefinitely, forming tumors.

  • Benign tumors: Remain at the original site.

  • Malignant tumors: Invade tissues and can metastasize to other parts of the body.

Molecular Biology of Cancer

Genetic Changes Leading to Cancer

  • Proto-oncogenes: Normal genes that stimulate cell growth; mutations convert them to oncogenes, causing excessive division.

  • Tumor-suppressor genes: Inhibit cell division; mutations reduce their function, contributing to cancer.

  • tumor supressor proteins

  • Ras proto-oncogene: Mutations lead to hyperactive Ras protein and increased cell division.

  • p53 tumor suppressor gene: Mutations prevent suppression of the cell cycle, allowing damaged cells to proliferate.

  • Multiple mutations are required for cancer development, often involving both oncogenes and tumor-suppressor genes.

  • Inherited mutations (e.g., BRCA1/BRCA2) can predispose individuals to certain cancers.

Summary Table: Cell Cycle and Cancer Genes

Gene Type

Normal Function

Cancer Effect

Proto-oncogene

Stimulates cell growth

Mutation increases activity, causing excessive division

Tumor-suppressor gene

Inhibits cell division, repairs DNA

Mutation reduces inhibition, allowing uncontrolled growth

Ras

Signal transduction for growth

Hyperactive protein stimulates division

p53

DNA repair, cell cycle arrest, apoptosis

Loss leads to proliferation of damaged cells

Additional info: The cell cycle is tightly regulated to ensure genetic stability. Disruption of these controls is a hallmark of cancer, and understanding these mechanisms is crucial for developing targeted therapies.

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