Summary of Cell Division: Mitosis and Meiosis

## Introduction Mitosis is the process by which a eukaryotic cell divides to produce two genetically identical daughter cells. It ensures faithful transmission of the parent cell's genome and supports growth, tissue maintenance, and regeneration in multicellular organisms. > **Definition:** The purpose of mitosis is the transmission of identical genomes to two daughter cells. ## Overview of the cell cycle The cell cycle has two main parts: Interphase and M-phase (mitosis). Interphase includes G1 (growth), S (DNA replication), and G2 (preparation). Mitosis (M-phase) is the stage when the nucleus divides (karyokinesis) and is followed by cytokinesis (division of the cytoplasm). ### Key sequential steps 1. Replication (DNA synthesis during S-phase) 2. Nuclear division (karyokinesis, mitosis) 3. Cell division (cytokinesis) > **Definition:** Interphase is the period when the cell is not undergoing mitosis; hereditary material is present as uncondensed chromatin. ## Stages of mitosis (digestible breakdown) ### Prophase - Chromosomes condense and become visible - The nuclear envelope begins to break down toward the end of prophase ### Prometaphase - Nuclear envelope breakdown (NEBD) completes - Microtubules attach to chromosomes at kinetochores and begin moving chromosomes toward the cell equator ### Metaphase - Chromosomes align at the metaphase plate - Sister chromatids are bioriented: each sister kinetochore is attached to microtubules from opposite spindle poles ### Anaphase - Cohesin linkages are cleaved and sister chromatids separate - Chromatids are pulled toward opposite poles by microtubule forces and by pole separation ### Telophase - Chromatids arrive at poles - New nuclear envelopes re-form and chromosomes decondense - Cytokinesis usually follows to split the cell into two > **Definition:** Centromere is the chromosomal region where kinetochores form. The kinetochore is the protein complex at the centromere required for microtubule attachment and force transduction. ## The mitotic spindle and chromosome movement - The mitotic spindle is built from microtubules and motor proteins (dynein and kinesins). - Prometaphase movement often involves pushing forces from motor proteins in addition to kinetochore activity. - Anaphase movement is dominated by pulling via microtubule depolymerization at kinetochores and by forces that push spindle poles apart. > **Definition:** Motor proteins: dynein moves toward microtubule minus-ends; many kinesins move toward plus-ends. ## Cohesion and its regulated cleavage - Sister chromatid cohesion is established during DNA replication by cohesion proteins (cohesins) and by DNA catenation (entanglement). - Cohesin on chromosome arms is removed in early mitosis; centromeric cohesin is protected until anaphase. - At anaphase onset, separase cleaves remaining cohesin, allowing sister chromatids to segregate. ## Checkpoints that ensure faithful division ### Restriction point / Start (G1) - Cyclin-dependent kinases (CDKs) activated by cyclins trigger transitions; high enough CDK activity at end of G1 commits the cell to S-phase. - The G1→S transition is effectively irreversible under normal conditions—the cell must complete mitosis to return to G1. > **Definition:** CDKs are enzymes that phosphorylate target proteins; their activity depends on binding to cyclins. ### DNA damage checkpoints - Monitor DNA integrity and completeness of replication - Arrest the cycle transiently to allow repair ### Mitotic checkpoint / Spindle Assembly Checkpoint (SAC) - Detects unattached kinetochores or lack of tension at kinetochores - If triggered, the SAC delays anaphase until all chromosomes are properly attached and bioriented ## Consequences of missegregation - Aneuploidy: abnormal chromosome number in daughter cells, common in many cancers - Micronuclei: small extra nuclei formed from missegregated chromosomes that failed to incorporate into daughter nuclei - Chromosome bridges and DNA breaks ca