mitosis
Summary
Mitosis is the process by which a single somatic cell divides to produce two genetically identical daughter cells, each with the same diploid (2n) chromosome number as the parent cell. It consists of four main phases—prophase, metaphase, anaphase, and telophase—preceded by S phase DNA replication. Mitosis is essential for growth, tissue repair, and cell replacement.
Detail
Mitosis occurs after the G2 phase of the cell cycle, following DNA replication in S phase, and is regulated by cyclins and cyclin-dependent kinases (CDKs), particularly the cyclin B-CDK1 complex which triggers entry into mitosis. Phases: (1) Prophase - chromatin condenses into visible chromosomes (each with two sister chromatids joined at the centromere), the nuclear envelope begins to break down, and the mitotic spindle starts forming from centrosomes. (2) Metaphase - chromosomes align at the metaphase plate (cell equator), attached to spindle fibers via kinetochores; this is monitored by the spindle assembly checkpoint to ensure proper attachment before proceeding. (3) Anaphase - sister chromatids separate and are pulled to opposite poles by shortening spindle fibers; triggered by activation of the anaphase-promoting complex (APC/C), which degrades securin, allowing separase to cleave cohesin proteins holding sister chromatids together. (4) Telophase - chromosomes decondense, nuclear envelopes reform around each set of chromosomes, and the spindle apparatus disassembles. Cytokinesis (division of the cytoplasm) typically overlaps with telophase, forming two separate daughter cells via a contractile actin-myosin ring in animal cells. Clinical relevance: Mitotic index (rate of cell division) is used to assess tumor aggressiveness—high mitotic activity is seen in malignancies and is a key histopathologic grading criterion (e.g., in breast cancer grading, sarcomas). Drugs targeting mitosis are used in cancer chemotherapy: microtubule inhibitors like vincristine/vinblastine (prevent spindle formation, arrest in metaphase) and paclitaxel/taxanes (stabilize microtubules, preventing depolymerization, arresting in metaphase). Errors in mitosis (e.g., nondisjunction, though more classically associated with meiosis) can lead to aneuploidy. Mitotic checkpoints are frequently dysregulated in cancer due to mutations in tumor suppressor genes (e.g., p53) or oncogenes affecting cell cycle regulators, contributing to uncontrolled proliferation. Understanding mitosis is foundational for cell biology and directly informs pathology (tumor grading), pharmacology (chemotherapeutic mechanisms), and genetics (chromosomal abnormalities).
Sources
- Robbins Basic Pathology
- Molecular Biology of the Cell (Alberts et al.)
- First Aid for the USMLE Step 1
- Lippincott Illustrated Reviews: Cell and Molecular Biology
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