Unit 8 Mitosis & Cell Cycle PDF

Mitosis & The Cell Cycle (Chapter 12) Sister chromatids Centromere 0.5 m  Cell Division - Overview Remember the characteristics of life: – Ability of organisms to reproduce is perhaps the best way to distinguish ‘life’ fr...

Mitosis & The Cell Cycle (Chapter 12) Sister chromatids Centromere 0.5 m  Cell Division - Overview Remember the characteristics of life: – Ability of organisms to reproduce is perhaps the best way to distinguish ‘life’ from ‘non-life’ Continuity of life based on reproduction of cells (cell division)  Cell Division - Overview Unicellular organisms: – Division of one cell reproduces the entire organism Multicellular organisms depend on cell division for: – Growth, development, repair  Cell Division - Overview Cell division is an integral part of the cell cycle: – Cell cycle charts the progress of a cell’s lifespan from its formation to its own division Recall cell theory: Every cell from a cell  Cell Division - Overview Most cell division results in daughter cells with genetic information (DNA) identical to the parent cell and to each other The exception is meiosis, a special type of division that produces sperm and egg cells (next chapter)  Organization of Genetic Material A cell’s DNA (its genetic information) Human Karyotype is collectively called its genome A genome can consist of – a single DNA molecule (common in prokaryotic cells), or – several DNA molecules (common in eukaryotic cells)  Eukaryotic Chromosomes DNA is packaged into chromosomes Chromosomes consist of chromatin, a complex of DNA and protein that condenses during cell division  Eukaryotic Chromosomes Every eukaryotic species has a characteristic number of chromosomes in each cell nucleus In humans, somatic cells (non-reproductive cells) have two sets of chromosomes (2 × 23 = 46 total) Gametes (reproductive cells: sperm and eggs) have half as many chromosomes as somatic cells  Chromosomes and Cell Division In preparation for cell division: – DNA is replicated – Chromosomes condense Each duplicated chromosome consists of two sister chromatids (joined copies of the original chromosome), held together by cohesin proteins  Chromosomes and Cell Division Centromere is the narrow ‘waist’ of the duplicated chromosome: – Location where the two chromatids are most closely attached  Chromosomes and Cell Division During cell division, sister chromatids separate and move into two nuclei Once they have been separated, the sister chromatids are called chromosomes  Types of Cell Division Eukaryotic cell division consists of: – Mitosis, the division of the genetic material in the nucleus, followed by… – Cytokinesis, the division of the cytoplasm Gametes are produced by a variation of cell division called meiosis – Meiosis yields non-identical daughter cells with only one set of chromosomes, half as many as the parent cell  Cell Cycle Phases Cell cycle consists of: – Interphase (cell growth and copying of chromosomes in preparation for cell division) – Mitotic (M) phase (mitosis and cytokinesis)  Cell Cycle Phases Interphase (90% of cell cycle) has 3 sub-phases: – G1 phase (‘first gap’) – S phase (DNA ‘synthesis’) – G2 phase (‘second gap’)  Cell Cycle Phases Cell grows during all three sub- phases of interphase, but chromosomes are duplicated only during S phase  Mitosis: Five Phases Prophase G2 of Interphase Centrosomes Prophase Prometaphase Fragments (with centriole Chromatin Early mitotic Aster of nuclear Nonkinetochore pairs) (duplicated) spindle Centromere envelope microtubules Prometaphase Metaphase Anaphase Plasma Telophase Nucleolus Nuclear envelope membrane Chromosome, consisting of two sister chromatids Kinetochore Kinetochore microtubule Metaphase Anaphase Telophase and Cytokinesis Metaphase Cleavage Nucleolus plate furrow forming Nuclear Spindle Centrosome at Daughter envelope one spindle pole chromosomes forming Cytokinesis is well underway by late telophase  Interphase G2 Nucleus: – Envelope is intact – Nucleolus is present (site of rRNA synthesis and ribosomal subunit assembly) Chromosomes: – Replicated – Not yet condensed Centrosome (microtubule- organization center): – Two centrosomes, each containing two centrioles Prophase Nucleus: – Nucleoli disappear – Envelope intact Chromosomes: – Begin to condense – Sister chromatids visible Centrosomes: – Begin moving to opposite poles – Begin forming mitotic spindle Prometaphase Nucleus: – Envelope degenerates Chromosomes: – Highly condensed – Interacting with microtubules (mt) – Kinetochore appears (proteins that attach centromeres to mts) Centrosomes: – Extend microtubules to attach to chromosomes (kinetochore mt) – Extend microtubules to interact with other mt (non-kinetochore mt) Metaphase Nucleus: – No evidence Chromosomes: – Line up on metaphase plate Centrosomes: – At opposite poles – Mt form ‘spindle apparatus’ – Kinetochore mt interact with kinetochores on sister chromatids – Non-kinetochore mt interact with mt from opposite pole Anaphase Nucleus: – No evidence Chromosomes: – Sister chromatids pull apart (separate into two chromosomes) – Centromeres lead the way Centrosomes: – At opposite poles – Kinetochore mt shorten – Non-kinetochore mt lengthen Telophase & Cytokinesis Nucleus: – Two daughter nuclei begin to form – Envelope rebuilds – Nucleolus reforms Chromosomes: – Decondense Centrosomes: – One per daughter cell Cytoplasm: – Formation of cleavage furrow pinches cell in two Phases of Mitosis  Phases of Mitosis 10 m G2 of Interphase Prophase Prometaphase Metaphase Anaphase Telophase and Cytokinesis Centrosomes Chromatin Fragments Nonkinetochore (with centriole pairs) (duplicated) Early mitotic Aster of nuclear microtubules Metaphase Cleavage Nucleolus spindle Centromere envelope plate furrow forming Plasma Nucleolus Nuclear membrane Chromosome, consisting Kinetochore Kinetochore Nuclear envelope of two sister chromatids microtubule Spindle Centrosome at Daughter envelope one spindle pole chromosomes forming  Mitotic Spindle Made of microtubules, controls chromosome movement during mitosis In animal, assembly of spindle microtubules begins in centrosome (microtubule organizing centre) Centrosome replicates during interphase; two resulting centrosomes migrate to opposite ends of the cell during prophase and prometaphase  Mitotic Spindle Aster (radial array of short microtubules) extends from each centrosome toward poles Collectively, the spindle includes centrosomes, spindle microtubules, and asters  Mitotic Spindle During prometaphase, some spindle microtubules attach to kinetochores and begin to move chromosomes – Kinetochore microtubules Kinetochores are protein complexes that form in association with the centromeres of chromosomes  Mitotic Spindle During anaphase, sister chromatids separate and move along the kinetochore microtubules toward opposite ends of the cell: – Motor proteins haul chromosome up microtubule (analogous to climbing a rope) Microtubules shorten by depolymerizing at their kinetochore ends  Mitotic Spindle Non-kinetochore microtubules from opposite poles overlap During anaphase they push apart from each other – Causes cell to elongate  Cytokinesis in Animal Cells Involves formation of a cleavage furrow – Contractile ring of actin microfilaments  Cytokinesis in Plant cells Involves formation of a cell plate – Vesicles containing cell wall materials 31  Mitosis in Plant Cells Chromatin Nucleus condensing 10 m Nucleolus Chromosomes Cell plate 1 Prophase 2 Prometaphase 3 Metaphase 4 Anaphase 5 Telophase Binary Fission Prokaryotes (bacteria and archaea) reproduce by type of cell division called binary fission Chromosome replicates (beginning at the origin of replication), and the two daughter chromosomes actively move apart Plasma membrane pinches inward, dividing cell into two  Regulation of the Cell Cycle Frequency of cell division varies with type of cell Cell cycle differences result from regulation at the molecular level Cell cycle appears to be regulated by specific chemical signals present in the cytoplasm Evidence for Cytoplasmic Signals S + G1 fusion – G1 cell enters S phase and synthesizes DNA  Evidence for Cytoplasmic Signals M + G1 fusion – G1 cell chromosome condenses (without duplicating DNA!!) – G1 cell forms spindle  Cell Cycle Control System The sequential events of the cell cycle are directed by a distinct cell cycle control system The cell cycle control system is regulated by both internal and external controls There are specific checkpoints where the cell cycle stops until a go-ahead signal is received  Checkpoints The G1, G2 and M checkpoints are three of the most important and best understood  Checkpoints If go-ahead signal at G checkpoint is 1 received: – Cell usually completes S, G and M phases and 2 divides  Checkpoints If go-ahead signal is not received: – Cell exits cell cycle – Cell switches into non- dividing phase known as G0  Checkpoints Checkpoint go- ahead signals are provided by two types of regulatory proteins interacting together: – Cyclins – Cyclin-dependent kinases (Cdk)  Cyclins & Cyclin-Dependent Kinases Cdk provides go-ahead signal, but cannot until it is attached to a cyclin Example of cyclin-Cdk complex is MPF – Maturation-promoting factor (‘M-phase’ promoting factor) – Triggers cell’s passage through G2 checkpoint to M phase Activity of cyclin-Cdk complexes fluctuate during cell cycle  MPF and G2 Checkpoints Cyclin accumulates in late S-phase Cyclin binds to Cdk to form active MPF MPF gives go-ahead signal at G2 to enter M-phase Cyclin is degraded, ending M-phase Cdk recycled, ready to bind cyclin in next S-phase 43  Internal Checkpoint Signals Checkpoint signals can originate from inside or outside of the cell Example of an internal signal: – Kinetochores not attached to kinetochore microtubules  Sends molecular signal to delay anaphase External Checkpoint Signals External signals include: – Growth factors – Anchorage dependence – Density-dependent inhibition  Growth Factors External signals (proteins) that stimulate cell division – E.g. platelet-derived growth factor (PDGF) stimulates division of human fibroblast cells  Platelet-Derived Growth Factor 1 A sample of human Scalpels connective tissue is cut up into small pieces. Petri dish 2 Enzymes digest the extracellular matrix, resulting in a suspension of free fibroblasts. 4 PDGF is added 10 m 3 Cells are transferred to to half the culture vessels. vessels. Without PDGF With PDGF  Density-Dependent Inhibition and Anchorage Dependence of Cell Division Most animal cells exhibit anchorage dependence – To divide, they must be attached to a surface Another external signal is density- dependent inhibition, in which crowded cells stop dividing – Demonstrated using cultured human fibroblast cells  Cancer Cancer cells exhibit neither density- dependent inhibition nor anchorage dependence  Cancer In addition, cancer cells do not respond normally to the control mechanisms exerted in the cell cycle – E.g. do not stop dividing when growth factors removed – E.g. do not use normal cell cycle checkpoints Cancer cells form tumours: – Masses of abnormal cells within otherwise normal tissue  Benign Tumours If abnormal cells remain at the original site, the lump is called a benign tumour: – Usually slow growing  Malignant Tumours and Metastasis Malignant tumours (‘cancer’) invade surrounding tissues in a process known as metastasis: – Cancer cells spread first to adjacent regions – Spread through lymphatic system and blood are common  Cancer Metastasis results in exporting of cancer cells to other parts of the body, where they may form additional tumors Localized tumors may be treated with high-energy radiation, which damages the DNA in the cancer cells Chemotherapies that target the cell cycle may be used to treat metastatic cancers, e.g. taxol  Summary  Purposes of cell division  Chromosome structure, sister chromatids  Cell cycle phases and sub-phases  Phases of mitosis (nucleus, chromosome, centrosome changes at each)  Mitotic spindle  Cytokinesis (animals and plants)  Binary fission  Cell cycle regulation  Checkpoints, Cyclin + Cdk  Internal and external control factors   INTERPHASE G1 S Cytokinesis Mitosis G2 MITOTIC (M) PHASE Prophase Telophase and Cytokinesis Prometaphase Anaphase Metaphase