Cell Cycle

Overview – Cell Cycle

•  Stages
  • interphase
    • G₁
      • purpose
        • cellular growth to prepare for DNA replication
          • synthesis of replication proteins, cyclin D
        • thymidine dimer repair
      • variable duration
      • can exit G₁ and enter G₀
      • chemotherapeutic agents that target G₀
        • cisplatin
        • nitrosoureas
        • antitumor antibiotics
        • alkylating agents
    • S
      • purpose
        • DNA replication
          • cell is 2N before S
          • cell is 4N after S
        • DNA proofreading
        • mismatch repair
      • constant duration
      • chemotherapeutic agents that target this stage
        • etoposide
        • 6-mercaptopurine
        • 6-thioguanine
        • methotrexate
        • cytarabine
        • hydroxyurea
    • G₂
      • purpose
        • cellular growth to prepare for cell division
        • mismatch repair (less active than in S phase)
      • variable duration
      • chemotherapeutic agents that target this stage
        • bleomycin
  • mitosis (M) 
    • steps
      • prophase
      • metaphase
      • anaphase
      • telophase
    • chemotherapeutic agents that target this stage
      • vinblastine
      • vincristine
      • paclitaxel
        • all drugs that affect microtubules
•  Regulation
  • control transitions between phases of cell cycle
    • G₁ checkpoint
      • at transition from G₁ to S
      • most important checkpoint
  • cyclins/cyclin-dependent kinases
    • cyclin D
      • produced during G₁
      • complex with Cdk4 (cyclin dependent kinase) at sufficient concentration
      • signal to enter S phase
  • tumor suppressors
    • requires mutation in both copies before neoplasia occurs
      • as opposed to oncogenes which require just one mutation
    • Rb
      • prevents cell from entering S phase
      • binds E2F to block its function as a transcription factor
      • named for retinoblastoma
    • P53
      • prevents cell from entering S phase
      • leads to inhibition of kinase activity of Cdk4 via p21
      • can induce apoptosis if cell damage is severe
        • via the BAX gene (proapoptotic)
          • inhibits BCL2 antiapoptosis gene
          • stimulates release of cytochrome c from mitochondria
• Cell types
  • permanent
    • enter G₀ and cannot leave
      • e.g. neurons, skeletal, cardiac muscle, RBCs
  • stable (quiescent)
    • enter G₀ and can leave when given appropriate stimulus
      • e.g. hepatocytes, lymphocytes
  • labile
    • never go to G₀
    • constant division with a condensed G₁
• e.g. bone marrow, skin, gut epithelium

Cell Cycle – Introduction

The cell cycle is the series of events that occur in a cell as it grows and divides into two daughter cells. It is a highly regulated process that is essential for the proper growth and development of all living organisms. The cell cycle consists of two main stages: interphase and mitosis.

Interphase is the stage of the cell cycle in which the cell grows and prepares for cell division. During interphase, the cell undergoes three sub-stages: G1, S, and G2. In G1, the cell grows and carries out normal metabolic functions. In S phase, DNA replication occurs, and the cell synthesizes new DNA. In G2, the cell continues to grow and prepares for cell division.

Phases of Cell Cycle

The cell cycle consists of two main stages: interphase and mitosis. Interphase is further divided into three phases: G1 phase, S phase, and G2 phase, while mitosis is divided into four stages: prophase, metaphase, anaphase, and telophase.

1. G1 phase: This is the first phase of interphase, during which the cell grows and carries out normal metabolic functions. This is also the longest phase of interphase and can last for several hours to several days, depending on the type of cell.
2. S phase: During this phase, the cell synthesizes new DNA and replicates its chromosomes. By the end of S phase, the cell contains twice the amount of DNA it had at the beginning of interphase.
3. G2 phase: This is the final phase of interphase, during which the cell continues to grow and prepare for cell division. The cell synthesizes new proteins and organelles and undergoes final checks to ensure that all DNA has been replicated properly.
4. Prophase: This is the first phase of mitosis, during which the chromatin condenses into visible chromosomes, and the nuclear envelope breaks down. The spindle apparatus, composed of microtubules and other proteins, begins to form.
5. Metaphase: During this phase, the chromosomes align at the equator of the cell, also known as the metaphase plate. The spindle fibers attach to the centromeres of the chromosomes.
6. Anaphase: During this phase, the sister chromatids separate and move to opposite poles of the cell, pulled by the spindle fibers.
7. Telophase: This is the final phase of mitosis, during which the nuclear envelope reforms around the chromosomes, and the cell begins to divide its cytoplasm. The chromosomes begin to uncoil, and the spindle apparatus disassembles.

After telophase, the cell enters cytokinesis, during which the cytoplasm divides to form two daughter cells, each with its own nucleus and set of chromosomes. Overall, the cell cycle is a highly regulated process that ensures proper growth and division of cells.

Studies

The study of the cell cycle is a crucial area of research in biology and medicine. Understanding the molecular mechanisms that regulate the cell cycle is essential for the development of new treatments for a wide range of diseases, including cancer.

Some of the key areas of study in the cell cycle include:

1. Cell cycle checkpoints: The cell cycle is regulated by a series of checkpoints that ensure the proper progression of the cell cycle. Defects in these checkpoints can lead to abnormalities in the cell cycle and the development of cancer. Researchers are studying these checkpoints to identify potential targets for cancer therapy.
2. Cyclins and cyclin-dependent kinases (CDKs): Cyclins and CDKs are proteins that regulate the cell cycle. They control the progression of the cell cycle by phosphorylating specific target proteins. Researchers are studying these proteins to understand their role in the cell cycle and identify potential targets for cancer therapy.
3. DNA replication and repair: DNA replication and repair are critical processes in the cell cycle. Defects in these processes can lead to mutations and the development of cancer. Researchers are studying these processes to develop new therapies for cancer and other diseases.
4. Cell cycle regulation in stem cells: Stem cells have unique cell cycle regulation mechanisms that allow them to self-renew and differentiate into various cell types. Researchers are studying these mechanisms to develop new therapies for regenerative medicine and tissue engineering.

Overall, the study of the cell cycle is a critical area of research that has the potential to lead to new treatments for a wide range of diseases.

Complication

Complications in the cell cycle can lead to a wide range of diseases, including cancer, genetic disorders, and developmental abnormalities. Some common cell cycle complications include:

1. DNA damage: The DNA in a cell can become damaged due to a variety of factors, including exposure to radiation, chemicals, or viruses. If the damage is not repaired properly, it can lead to mutations and other abnormalities that can result in cancer or other diseases.
2. Chromosomal abnormalities: Chromosomal abnormalities can occur when there are errors in the segregation of chromosomes during mitosis. This can result in the loss or gain of entire chromosomes or parts of chromosomes, which can lead to genetic disorders and developmental abnormalities.
3. Cell cycle arrest: The cell cycle can be arrested at various checkpoints due to factors such as DNA damage or nutrient depletion. If the cell cycle arrest is prolonged, it can lead to cell death or abnormal cell growth.
4. Aberrant cell division: Aberrant cell division can occur when the cell cycle is not properly regulated, leading to abnormal cell growth and the formation of tumors.
5. Cell senescence: Senescence is a state in which cells stop dividing and undergo changes in gene expression and metabolism. While senescence is a normal part of aging, it can also be triggered by various factors, including DNA damage, telomere shortening, and oncogene activation. Abnormal senescence can contribute to aging-related diseases and cancer.

Understanding the molecular mechanisms that regulate the cell cycle and the factors that contribute to cell cycle complications is critical for the development of new therapies for a wide range of diseases.

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