LC

7.2 Cell Cycle and Cell Division Notes

  • Cell division definition:

    • One parent cell divides to form two new cells called daughter cells. It is fundamental for growth, tissue repair, and reproduction in multicellular organisms, and for propagation in unicellular ones. This process ensures the accurate distribution of genetic material to daughter cells.

    • Involves duplication and separation of cell parts, including chromosomes and organelles.

    • Occurs in both prokaryotic and eukaryotic cells, but the process differs significantly due to cellular complexity.

  • Prokaryotic vs. eukaryotic cells:

    • Prokaryotes:

    • Simpler structure with a single circular chromosome, no membrane-bound nucleus, and few organelles.

    • Cell division occurs via binary fission, a rapid and relatively simple process involving the replication of the single circular chromosome and the subsequent division of the cell. This is a form of asexual reproduction.

    • Eukaryotes:

    • Contain multiple linear chromosomes organized within a true nucleus and possess many membrane-bound organelles.

    • Their complex cell division, involving mitosis (for nuclear division in somatic cells) and meiosis (for sexual reproduction in germline cells), ensures precise chromosome segregation.

    • Cell cycle includes distinct phases for growth, DNA synthesis, and division.

  • The cell cycle concept:

    • A repeating series of events including growth, DNA synthesis, and cell division.

    • In prokaryotes, the cycle is simpler: cell grows, DNA replicates, and the cell divides.

    • In eukaryotes, the cycle is more complex and includes distinct, highly regulated phases to manage their larger, linear chromosomes and complex organelle systems.

  • Eukaryotic cell cycle overview:

    • The mitotic phase (M) includes mitosis (nuclear division) and cytokinesis (cytoplasm division), collectively resulting in two daughter cells.

    • The interphase comprises the G1, S, and G2 phases, during which the cell grows, its DNA is replicated, and preparations for division occur.

    • Cells spend most of their life, typically 90% or more, in interphase.

  • Interphase details:

    • Growth Phase 1 (G1):

    • The cell spends much of its life here; rapid growth and routine metabolic activities occur. It monitors its internal and external environment to decide whether to commit to division. Key factors include sufficient resources, appropriate size, and absence of DNA damage.

    • Biosynthetic activities are high; synthesis of amino acids, proteins, and nucleotides needed for DNA replication occurs.

    • If a cell is not dividing, or if conditions are not met, it may stay in G1 or exit the cycle to enter G0 (a resting phase).

    • G0 (resting phase):

    • Non-dividing cells in multicellular organisms may enter G0 from G1.

    • Some cells may remain in G0 for long periods or indefinitely (e.g., mature neurons and muscle cells, which are terminally differentiated). Hepatocytes (liver cells) can re-enter the cycle under specific stimuli (e.g., injury or regeneration).

    • Cellular senescence:

    • Normal diploid cells lose the ability to divide after a finite number of cell divisions (about 50 in human somatic cells, governed by the Hayflick limit). This state is often triggered by telomere shortening, DNA damage, or strong growth-inhibitory signals. Senescent cells remain metabolically active but lose the ability to proliferate, playing roles in aging and tumor suppression. This process is called cellular senescence.

    • Synthesis Phase (S):

    • DNA replication occurs; the DNA is copied to generate two new complementary strands. Each chromosome is faithfully replicated to form two identical sister chromatids, which remain joined at the centromere. This replication is semi-conservative, meaning each new DNA molecule consists of one original strand and one newly synthesized strand.

    • The amount of DNA doubles during S phase, though the cell remains diploid.
      \text{Notation: before S, the cell has 2C DNA content; after S, it has 4C DNA content, while chromosome number remains } 2n.
      \text{DNA content: } 2C \rightarrow 4C \quad \text{(chromosome number remains } 2n \text{)}

    • Growth Phase 2 (G2):

    • A shorter growth period where many organelles are reproduced or manufactured. This is a critical 'safety gap' where the cell reviews the success of DNA replication and ensures any damage is repaired.

    • Cellular components required for mitosis, such as microtubules for the mitotic spindle, are produced. Structural proteins and components necessary for spindle formation, like tubulin monomers, are synthesized to prepare for the accurate segregation of chromosomes during mitosis.

  • The mitotic phase (M):

    • Before division, all DNA has been replicated and organelles duplicated during interphase.

    • Mitosis: division of the nucleus, a continuous process divided into several distinct stages: prophase, prometaphase, metaphase, anaphase, and telophase, each ensuring accurate segregation of sister chromatids.

    • Cytokinesis: division of the cytoplasm, which typically overlaps with the later stages of mitosis (anaphase and telophase), resulting in two separate daughter cells. Cytokinesis differs in animal cells (involving a contractile ring forming a cleavage furrow) and plant cells (involving the formation of a cell plate that develops into a new cell wall).

    • Note: This description aligns with the concept that cytokinesis occurs in prokaryotic cells as well, though in prokaryotes the process is not the same as eukaryotic cytokinesis.

  • Key concepts: checkpoints and regulation

    • The cell cycle is regulated mainly by signaling regulatory proteins, primarily through a complex network of cyclin-dependent kinases (CDKs) and their activating partners, cyclins. Different cyclin-CDK complexes become active at specific phases, driving progression.

    • Checkpoints ensure the cell completes the previous phase accurately and is ready before moving on to the next.

    • Main checkpoints:

    • G1 checkpoint: Often referred to as the 'restriction point' in mammalian cells, this is the most critical checkpoint. It assesses cell size, nutrient availability, growth factor presence, and DNA integrity. If conditions are not favorable or if DNA is damaged, the cell will halt or enter G0. If passed, the cell commits to division.

    • S checkpoint: Determines if DNA replication occurred properly and completely, and monitors for DNA damage. It ensures that only fully replicated and undamaged DNA proceeds to G2.

    • M phase checkpoint (Spindle Assembly Checkpoint, SAC): Ensures chromosomes are properly attached to the mitotic spindle microtubules at the metaphase plate before anaphase onset. This prevents aneuploidy (abnormal chromosome number) in daughter cells by ensuring equal distribution of genetic material.

    • These checkpoints help prevent progression to the next phase until the cell is ready, thereby maintaining genomic stability.

  • Cancer and the cell cycle

    • Cancer results from loss of regulation in the cell cycle due to accumulated DNA damage and mutations. The underlying cause often involves mutations in two main classes of genes: proto-oncogenes (which, when mutated, become oncogenes promoting uncontrolled cell division) and tumor suppressor genes (which normally inhibit cell division or trigger apoptosis).

    • Damage leads to mutations in genes that regulate the cycle (e.g., p53, often called 'the guardian of the genome'), causing uncontrolled cell division.

    • Rapid, unregulated division can form tumors, which consume nutrients and space, damaging tissues and organs through compression or invasion.

    • In some cancers (e.g., certain bone marrow cancers like leukemia), abnormal and nonfunctional cells are produced even without forming a solid tumor.

  • HeLa cells and Henrietta Lacks: a case study in biology and ethics

    • Henrietta Lacks (1951): Cells taken from her aggressive cervical tumor without her knowledge or consent were used for research.

    • HeLa cell line: The first immortal human cell line; these cells keep dividing indefinitely in culture and were extensively cultured worldwide since 1953. The cell line's ability to propagate indefinitely under normal lab conditions made it invaluable for high-throughput screening and standardization in research.

    • HeLa cells have been used in thousands of studies and contributed to many medical advances (e.g., development of the polio vaccine by Jonas Salk; cancer and AIDS research; space biology experiments; early human cell cloning and gene mapping; understanding viruses and developing in vitro fertilization techniques).

    • HeLa cells enabled large-scale commercial production for research.

    • The 2010 book The Immortal Life of Henrietta Lacks by Rebecca Skloot popularized her story; a film adaptation was planned by Oprah Winfrey and collaborators.

    • Ethical implications:

    • The case highlights profound issues of informed consent, tissue ownership, patient privacy, and equitable benefit sharing from research. It instigated widespread reforms in bioethics, leading to stricter informed consent requirements, guidelines for tissue donation, and ongoing discussions about control over biological materials in research.

    • Despite the immense scientific impact, Lacks’ family experienced poverty and lacked access to her medical information, highlighting long-standing equity concerns and historical abuses in biomedical research.

  • Review questions (key takeaways)

    • 1) What are the two main phases of the cell cycle in a eukaryotic cell?

    • Interphase and the mitotic phase (M).

    • 2) Describe the three phases of interphase in a eukaryotic cell.

    • G1: cell growth and normal functions; high biosynthetic activity; prepares for DNA replication; may enter G0 if not dividing or if conditions are unfavorable.

    • S: DNA replication occurs, doubling the DNA content (each chromosome forms two sister chromatids); chromosomes are copied but cell remains 2n.

    • G2: preparation for mitosis; further growth; organelles and mitotic apparatus (e.g., spindle components like tubulin) are produced; critical checks for DNA integrity and successful replication.

    • 3) Explain how the cell cycle is controlled.

    • Regulatory proteins (cyclins and cyclin-dependent kinases, CDKs) control the cycle, and specific checkpoints ensure the cell completes the current phase accurately and is ready before moving on, monitoring for cell size, DNA damage, and chromosome attachment.

    • 4) How is cancer related to the cell cycle?

    • Cancer results from uncontrolled cell division due to mutations in cell-cycle regulatory genes (like proto-oncogenes and tumor suppressor genes), leading to failed checkpoints and potentially tumor formation.

    • 5) What are the two major steps of cell division in a eukaryotic cell?

    • Mitosis (nuclear division) and cytokinesis (cytoplasm division).

    • 6) In which phase of the eukaryotic cell cycle do cells typically spend most of their lives?

    • Interphase.

    • 7) Which phases of the cell cycle will have cells with twice the amount of DNA? Explain your answer.

    • S phase (after replication), G2 phase, and early M phase (prophase, metaphase, anaphase before cytokinesis completes). During the S phase, DNA replication occurs, doubling the DNA content from 2C \text{ to } 4C (while the chromosome number remains 2n as sister chromatids are still joined).

    • 8) If there is damage to a gene that encodes for a cell cycle regulatory protein, what might happen? Explain.

    • The cell cycle could proceed unchecked, leading to uncontrolled division and potentially cancer, as checkpoints may fail to halt progression despite damage. This can result in the accumulation of mutations and abnormal cell proliferation.

    • 9) True or False. Cells go into G0 if they do not pass the G1 checkpoint.

    • True.

    • 10) In which phase within interphase does the cell make final preparations to divide? A. Mitosis B. Cytokinesis C. G2 D. S

    • C. G2 (G2 is the final preparation stage before mitosis, including necessary syntheses and final checks).

    • 11) What were scientists trying to do when they took tumor cells from Henrietta Lacks? Why did they specifically use tumor cells to try to achieve their goal?

    • They were trying to grow human cells in the lab for testing and research; tumor cells were used because they possess mutations that allow them to divide rapidly and continuously, behaving as immortal cells that can be maintained in culture, unlike normal human cells that undergo senescence.

  • Explore more

    • Explore More link: https://bio.libretexts.org/link?16754#Explore_More

  • Ethical and practical implications to remember

    • Tissue ownership and consent in biomedical research, emphasizing the rights and autonomy of individuals.

    • Balance between scientific advancement and the rights and welfare of patients and families, ensuring equitable benefits.

    • Modern ethical guidelines, including the Common Rule in the US, mandate informed consent for research involving human subjects and their biological materials, aiming to prevent similar historical abuses.

  • Quick connections to foundational principles

    • The cell cycle integrates growth, DNA replication, and division, ensuring genetic material is accurately copied and distributed, demonstrating the principle of genetic continuity.

    • Regulation by checkpoints safeguards against DNA damage and improper division, illustrating biological control mechanisms and the importance of cellular homeostasis.

    • Cancer highlights the devastating consequences of mutations in regulatory networks that control the cycle, linking cellular processes to disease pathology.

    • The cell cycle illustrates the central dogma of molecular biology by carefully regulating DNA replication and gene expression during growth and division.

  • Key terminology to review

    • Chromosome number (2n, diploid); DNA content (C values: 2C, 4C);

    • Interphase (G1, S, G2); M phase (Mitosis and Cytokinesis);

    • G0 (resting); cellular senescence; telomere shortening; tumor; HeLa cells; immortal cell line; cyclin-dependent kinases (CDKs); cyclins; proto-oncogenes; tumor suppressor genes; cleavage furrow; cell plate; aneuploidy; semi-conservative replication; sister chromatids; centromere.

  • Notation recap

    • DNA content progression during the cycle: 2C \rightarrow 4C during S phase, while chromosome number remains 2n. This indicates that the amount of DNA doubles, but the number of centromeres (and thus chromosomes) does not change until anaphase in mitosis.

    • G0 is the resting state outside active cycling.

  • Summary takeaway

    • The eukaryotic cell cycle is a highly intricate and tightly regulated sequence of phases (Interphase: G1, S, G2; Mitotic phase: Mitosis and Cytokinesis) coordinating cellular growth, precise DNA replication, and equitable division. A sophisticated network of checkpoints, involving cyclin-CDK complexes, ensures the fidelity of these processes, safeguarding against errors like DNA damage and improper chromosome segregation. Dysregulation of this cycle, often due to mutations in proto-oncogenes or tumor suppressor genes, is a hallmark of cancer. Historical contexts such as the Henrietta Lacks case with HeLa cells highlight profound ethical challenges regarding informed