Cell Cycle, Mitosis and Meiosis 2025 PDF

WE MAKE DOCTORS Cell cycle, mitosis and meiosis Ana Gabriela Colima Fausto, PhD Learning objectives Outline the characteristics and phases of the cell cycle: G0,G1,S,G2,M Identify the cell cycle checkpoints Describe the mitosis and meiosis processes and their phases Ex...

WE MAKE DOCTORS Cell cycle, mitosis and meiosis Ana Gabriela Colima Fausto, PhD Learning objectives Outline the characteristics and phases of the cell cycle: G0,G1,S,G2,M Identify the cell cycle checkpoints Describe the mitosis and meiosis processes and their phases Explain spermatogenesis and oogenesis processes CELL CYCLE The series of events that take place in a cell leading to its division and duplication of its DNA During this period, the contents of the cell must be accurately replicated. To divide, a cell must grow, copy its genetic material (DNA), and physically split into two daughter cells. Cells perform these tasks in an organized, predictable series of steps that make up the cell cycle. Cycle Interphase + M phase CELL CYCLE CELL CYCLE DNA replication and protein synthesis take place during interphase. G1: synthesis of RNA and proteins takes place Synthesis: DNA replication G2: DNA repair takes place, and the cell prepares for mitosis G0: Cell cycle arrest MITOSIS Mitosis a is division that produces two daughter cells with the same genetic component as the parent cell. Chromosomes replicated during the S phase are divided in such a way as to ensure that each daughter cell receives a copy of every chromosome. 1-2 hours Prophase Prophase occupies over half of mitosis. Chromosomes condense into compact structures Nuclear membrane breaks down. Duplication of centrosome Spindle fibers begin to form, radiating from two centrioles 46 chromosomes 92 chromatids Centromere ≠ Centriole ≠ Centrosome Prometaphase The chromosomes, led by their centromeres, migrate to the equatorial plane. The spindle fibres bind to a structure associated with the centromere of each chromosome called a kinetochore. Individual spindle fibres bind to a kinetochore structure on each side of the centromere. Metaphase The chromosomes reach their most highly condensed state during metaphase During metaphase, the spindle fibers begin to contract and pull the centromeres of the chromosomes, which are now arranged along the middle of the spindle (the equatorial plane of the cell). Clinical diagnosis of chromosomal abnormalities: Karyotype Anaphase The shortest stage of mitosis The centromere of each chromosome split and the sister chromatids of each chromosome are pulled apart and move to the opposite ends of the cell 92 chromatides, half lying near one side of the cell and half near the other side Telophase The nuclear membrane reforms around the chromosomes grouped at either pole of the cell. The chromosomes uncoil and become diffuse. The spindle fibres disappear. Cytokinesis Two diploid daughter cells, both identical to the original cell, have been formed, each one with a set of 46 chromosomes. The length of the cell cycle In rapidly dividing cells such as those of epithelial tissue (found, for example, in the lining of the intestines and in the lungs), the cycle may be completed in less than 10 hours. Other cells, such as those of the liver, might divide only once each year or so. Some cell types, such as skeletal muscle cells and neurons, largely lose their ability to divide and replicate in adults. Mammals: 16 hours Plants: 29 hours Yeasts: 1.5 to 3 hours Frog embryo: 30 minutes Checkpoints Cells divide in response to important internal and external cues The cell must respond to extracellular stimuli that require increased or decreased rates of division. Complex molecular interactions mediate this regulation: CDK- cyclins CDK: cyclin-dependent kinases , a family of kinases that phosphorylate other regulatory proteins at key stages of the cell cycle. Cyclins: proteins that are synthesized at specific cell-cycle stages and are then degraded when CDK action is no longer needed Kinases inhibitors: Inhibit the complex Ensure proper division of the cell Checkpoints G1 restriction point Point of no return, complete the cycle or apoptosis. Environmental conditions are the ideal ones, the presence of a high energy state and the access to metabolites necessary for the synthesis of biomolecules. CDK4 and CDK6 with Cyclin D E2F transcription factor Rb protein KIN4 (p16) G1/S checkpoint Check that the cell has grown enough and if DNA is damaged Levels of p53: DNA damage Apoptosis CDK2 with cyclin E Inhibitors:p53,p21 G2/M checkpoint DNA damage or incomplete replication Extracellular environment CDK1 with cyclin A and B: mitosis promotor factor induce the assembly of the mitotic spindle induces chromatin condensation Activation of condensins Inhibitor:p53 and p21 Mitosis checkpoint From metaphase to anafase All chromosomes attached to the mitotic spindle Kinetochores APC/CDC20 Securins Separase Endomitosis: Poliploidy Endoreduplication: Politomic chromosomes Meiosis Cell division that produces haploid sex cells or gametes (which contain a single copy of each chromosome) from diploid cells (which contain two copies of each chromosome) Meiosis I and Meiosis II Preceded by DNA replication 46 chromosomes, 92 Chromatids Meiosis I Prophase I: The homologous chromosomes pair and exchange DNA to form recombinant chromosomes Leptotene Zygotene Pachytene Diplotene Diakinesis Prometaphase I Spindle apparatus formed, and chromosomes attached to spindle fibres by kinetochores. Crossing over Meiosis I Metaphase I: Completion of spindle formation and alignment of the bivalents (Homologous pairs of chromosomes) Bivalents arranged as a double row along the metaphase plate Anaphase I: The homologous chromosomes in each bivalent are separated and move to the opposite poles of the cell Meiosis I Telophase I The chromosomes become diffuse and the nuclear membrane reforms. Cytokinesis occurs during this phase The two daughter cells each contain the haploid number of chromosomes , and each chromosome has two sister chromatids. 1 Cell: 23 chromosomes, 46 chromatids Reductive division 2n:1n  Meiosis II separates each chromosome into Meiosis II two chromatids Equational division 1n:1n Similar to mitosis Prophase II The chromosomes thicken as they coil, the nuclear membrane disappears, and new spindle fibers are formed Metaphase II The spindle fibers pull the chromosomes into alignment at the equatorial plane.  Anaphase II Meiosis II Chromatids are separated The newly separated sister chromatids might not be identical Telophase II The chromosomes reach opposite poles of the cell. There they begin to uncoil. New nuclear membranes are formed around each group of chromosomes, and cytokinesis occurs. 4 haploid cells Cell: 1 chromosome: 1 chromatid Genetic diversity Spermatogenesis 2n (46 Chromosomes) 2n (46 Chromosomes, 92 chromatids) 1n (23 Chromosomes, 46 chromatids) 1n (23 Chromosomes) 1n (23 Chromosomes) Oogenesis 1 million primary oocytes 400 000-500 000 primary oocytes puberty 400 -500 secundary oocytes 1 ovum: 3 polar bodies  Mitosis and Meiosis errors Mitosis Cancer Non disjunction:mosaicism Meiosis Non disjunction Chromosomal abnormalities: aneuploidies Bibliography Lynn B. Jorde, John C. Carey, Michael J. Bamshad· Medical Genetics. 6th Edition. Elsevier, 2019.