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Cell Division DNA Represents Information – the information is organized at various levels of structure: genome chromosomes decreasing scale genes codons nucleotides Definitions of Gene: 1) A sequence of DNA/nucleotides/codons that specifies the primary structure of a protein (or a polypeptide); this...

Cell Division DNA Represents Information – the information is organized at various levels of structure: genome chromosomes decreasing scale genes codons nucleotides Definitions of Gene: 1) A sequence of DNA/nucleotides/codons that specifies the primary structure of a protein (or a polypeptide); this is often called the “one gene-one protein” definition, or alternatively , the “one gene-one polypeptide” definition. 2) Sections of DNA that that code for a useful product, e.g. protein/polypeptide, tRNA, rRNA, other forms of RNA. Chromosome – Typically 100s to 1000s of genes per chromosome. Genome – Total hereditary endowment of DNA. Chromosomes – Composed of chromatin (DNA-protein complex). DNA (= info) protein (structural role) OpenStax Biology 2e Cell Division Organization of DNA and Chromatin Double-stranded DNA wraps around histone proteins to form nucleosomes that create the appearance of “beads on a string.” The nucleosomes are coiled into a 30-nm chromatin fiber. When a cell undergoes mitosis, the chromosomes condense even further. Maximum coiling occurs in the condensed chromosomes. There won’t be any test questions about nucleosomes or histones or levels of coiling. Condensed chromosome. Chromosomes are not usually in this form (although most photos of chromosomes show this form). Condensed chromosomes occur in only certain stages of the cell cycle (M phase) and during stages of meiosis. Cell Division • Chromatin has various levels of organization. • There are coils composed of coils composed of coils. • Condensed chromosomes (bottom right) are not the typical form. • Condensed chromosomes have maximum coiling. There won’t be any test questions about nucleosomes or histones or levels of coiling. https://www.nature.com/scitable /topicpage/dna-packagingnucleosomes-and-chromatin310/ Cell Division • “Chromosomes are threadlike structures made of protein and a single molecule of DNA that serve to carry the genomic information from cell to cell.” https://www.genome.gov/genetics-glossary/Chromosome • Number of chromosomes varies between species, but is constant within species; -e.g. lake trout and hamsters have a different number of chromosomes, but all lake trout have the same (defined) number of chromosomes -chromosome number is characteristic of the species; e.g. all lake trout have 84 chromosomes, and all hamsters have 22 chromosomes -humans have 46 chromosomes • Also, within a species, the same genes are in the same place (same physical location) on the same chromosome; -the physical location of a gene on a chromosome = the locus -locus – singular -loci – plural The locus is the physical location of a gene on a chromosome. In the example on the right, all members of a species would have gene “B” in the same physical location on the same chromosome. Modified from https://www.genome.gov/genetics-glossary/Allele Cell Division • “Cell Theory” states that all cells come from pre-existing cells. • The pre-existing cells have a genome -genome = total hereditary endowment of DNA; total hereditary endowment of information • Mitotic cell division leads to “daughter cells” • The daughter cells must have the same genome/info as the original cell, and as each other;  conservation of genetic information through each round of cell division • The daughter cells can undergo cell division;  the daughter cells of the daughters are genetically identical • Does not matter how many rounds of cell division occur;  each round produces genetically identical daughter cells G2 of “cell cycle” (we’ll get to that) https://medlineplus.gov/genetics/understanding/howgeneswork/cellsdivide/ Cell Division • The daughter cells are genetically identical to each other and to the mother cell. • Conservation of genetic information. parent/mother cell cell division • This could be cell division in a multicellular organism. • Or cell division in a unicellular organism. two daughter cells Cell Division • Consider the growth of a multicellular organism. • Start with a Zygote (one cell, product of fertilization). Embryo (not shown in diagram) Juvenile Adult • The organism grows larger via cell division (many, many rounds). • Zygote (one cell) has genetic information; all the subsequent cells must have the same info. • All the cells in the adult have the same genetic information as each other (although they may do different things with it) and as the zygote;  conservation of genetic information Growth of a fuzzy grelber from zygote  juvenile  adult (the embryo stage is not shown in the diagram) (Fuzzy grelbers are fictitious insectivorous mammals.) Cell Division • Chromosomes spend most of their time in the non-condensed state. • However, during mitosis the chromosomes condense (they really coil; this coil is different from the double helix, which always exists). • Chromosomes in the condensed state always have sister chromatids, Diagram of a replicated and condensed metaphase eukaryotic chromosome. (1) Chromatid – one of the two identical parts of the chromosome after S phase. (2) Centromere – the point where the two chromatids touch, and where the microtubules attach. (3) Short arm. (4) Long arm. By !File:Chromosome-upright.pngOriginal version: Magnus Manske, this version with upright chromosome: User:Dietzel65Vector: derivative work Tryphon - Own work based on: Chromosomeupright.png, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=5285797 Cell Division tangled, non-condensed chromosomes Analogous to a pot of spaghetti: https://www.ohmyfoodrecipes.com/cantonese-soy-saucepan-fried-noodles/ nuclear envelope (double membrane) This is the standard state of chromosomes. These tangled chromosomes may or may not have sister chromatids. G1  no sister chromatids; G2  sister chromatids (we will talk about G1 and G2). Cell Division A diagram of a one condensed chromosome composed of sister chromatids. • This is one chromosome. • The sister chromatids are identical in every way. • Non-condensed chromosomes may also have sister chromatids, or they might not (depends in the stage of the cell cycle). • If sister chromatids are present, the sister chromatids are joined at the centromere (2). • During mitotic cell division, which is what we are talking about right now, each daughter cell receives one of the sister chromatids;  genetic info is conserved • But what happens when the daughter cells want to sister chromatid #1 sister chromatid #2 undergo cell division?  need to duplicate the genetic info prior to one chromosome division  chromosomes with two chromatids are a prerequisite for cell division Cell Division • Chromosome replication is prerequisite for cell division. • Need to go from chromosome composed of a chromatid  chromosome with two chromatids. • Nuclear enzymes: DNA polymerases and associated enzymes; -DNA polymerases make the DNA copies, but need help from other enzymes • Make copies of DNA (using the standard rules for complementary bases)  identical sister chromatids. • Nucleus has a pool of DNA nucleotides, used by DNA polymerase. A = T OpenStax Biology 2e G≡C You don’t need to know the details of this slide. One chromatid becomes two chromatids. No increase in the number of chromosomes. Cell Division • Make copies of DNA (using the standard rules for complementary bases)  identical sister chromatids. • Both strands of the chromosome are used as templates for making new strands. • Each resulting sister chromatid thus contains one original strand and one new strand. • Example DNA template strand: ATTGGCCTAGC A=T New strand produced by DNA polymerase: TAACCGGATCG G≡C Original doublestranded DNA; no sister chromatids OpenStax Biology 2e Sister chromatids being produced. You don’t need to know the details of this slide. Cell Division – Cell Cycle • The cell cycle is a defined process (series of events) that most cells go through; -although some cells stop part way through the cycle • Tightly regulated. • During the majority of the cell cycle the chromosomes are non-condensed; = interphase • Interphase has three sub-phases (G1, S, G2). (Diagram on next slide.) • One of the things that happens during interphase is that DNA polymerase duplicates the chromosomes; -chromosomes composed of one chromatid  chromosomes composed of sister chromosomes -keep in that this ≠ changing the number of chromosomes G1 One chromatid per chromosome S Chromosome duplication G2 Two chromatids per chromosome • Chromosomes condense during the M phase of the cell cycle. • The M phase may be subdivided into two sub-phases: 1) mitosis = evenly dividing the genetic material 2) cytokinesis = cell division Cell Division – Cell Cycle • Chromosomes are condensed only during the M phase. Interphase chromosome duplication (synthesizing of chromatids); non-condensed chromosomes S G2 G1 two chromatids per chromosome; non-condensed chromosomes one chromatid per chromosome; non-condensed chromosomes M Phase Mitosis = dividing of DNA between daughter cells; chromosomes are condensed Mitosis in (Not Very Good) Pictures nucleus nuclear envelope plasma membrane Cell in G2 phase of the cell cycle. Chromosomes are non-condensed, and are composed of two chromatids per chromosome. condensed chromosomes (w sister chromatids) nuclear envelope Early part of the M phase of the cell cycle. Chromosomes are condensed, and the nuclear envelope will soon disintegrate. spindle contracts; sister chromatids pulled to opposite ends plasma membrane Mitosis in (Not Very Good) Pictures Some parts of the spindle are attached to the centromeres chromosome (one chromatid) spindle cleavage furrow Later in the M phase. Nuclear envelope has disintegrated. Spindle (microtubules) has formed, and chromosomes are lined up (singly) at the centre of the cell. Spindle contracts, pulling sister chromatids to opposite ends. End of the M phase and beginning of cytokinesis (cell division). Chromosomes are composed of only one chromatid because sister chromatids have been separated. In animal cells the division occurs via a cleavage furrow. Mitosis in (Not Very Good) Pictures • End result: two genetically identical daughter cells. • The daughter cells are in the G1 phase of the cell cycle, and chromosomes are noncondensed and composed of one chromatid per chromosome. • Further rounds of cell division are not possible until the chromosomes have been duplicated in the S phase of the cell cycle. • Duplicated chromosomes (produced in the S phase) contain 2 chromatids per chromosome (note: there is no change in the number of chromosomes in the S phase). nucleus plasma membrane M Phase of the Cell Cycle OpenStax Biology You don’t need to the stages/phases of the M phase/mitosis (although many students will already know the stages in great detail). M Phase of the Cell Cycle Centromere – specialized zone of DNA where sister chromatids are held together; always present Kinetochores – composed of proteins; produced during the M phase; two kinetochores per centromere; spindle microtubules attach to the kinetochores OpenStax Biology During prometaphase, mitotic spindle microtubules from opposite poles attach to each sister chromatid at the kinetochores. In anaphase, the connection between the sister chromatids breaks down, and the microtubules pull the chromosomes toward opposite poles. M Phase of the Cell Cycle During cytokinesis in animal cells, a ring of actin microfilaments (part of the cytoskeleton) forms at the metaphase plate. The ring contracts, forming a cleavage furrow, which divides the cell in two. In plant cells, Golgi vesicles coalesce at the former metaphase plate, forming a phragmoplast. A cell plate formed by the fusion of the vesicles of the phragmoplast grows from the center toward the cell walls, and the membranes of the vesicles fuse to form a plasma membrane that divides the cell in two. You do not need to know about the phragmoplast, or anything else about plant cell division. OpenStax Biology Cell Division – Back to the Cell Cycle • There is another phase to the cell cycle in some cells: the G0 phase (called “G zero” or “G nought”). • G0 is often described as a “resting phase”. • Cells may enter G0 from G1, and can optionally re-enter the cell cycle in G1. • G0 is an optional detour from G1. • The detour may be temporary or permanent (depends on cell type). G0 G0 is optional Cell Division – Back to the Cell Cycle • Some cells spend a long time in G0;  they are simply not dividing • Some cells are permanently in G0;  these cells are fully/terminally differentiated • Cell types that that enter G0 permanently include: -neurons -some liver cells -some kidney cells  these cells are sometimes referred to as “post-mitotic” cells • Some cell types rarely or never enter G0 because continually dividing; -e.g. epithelial cells (cells that produce the outer surfaces of organs, including the skin) Cell Division - Regulation • The cell cycle is tightly regulated. • In multicellular organism, can’t have any old cells doing cell division at any old time. • Cancer is partly a disease of cell cycle mis-regulation or de-regulation;  unchecked/unregulated cell division leads to tumours • A lot cancer research focuses on cell cycle regulation. Cell Cycle also has “Checkpoints” = key control points of the cell cycle • Checkpoints are present in order to make sure that everything is working properly; especially as related to DNA. The cell cycle is controlled at three checkpoints. The integrity of the DNA is assessed at the G1 checkpoint. Proper chromosome duplication is assessed at the G2 checkpoint. Attachment of each kinetochore to a spindle fiber is assessed at the M checkpoint. You do not need to remember exactly where the checkpoints occur. Cell Division - Regulation Cell Cycle “Checkpoints” • It’s important that actively dividing cells accurately copy/duplicate the DNA, and the chromosomes must be evenly divided among daughter cells (each daughter cell receives a chromatid);  the daughter cells must have the genetic info as the mother cell and as each other • Mistakes in duplication or in sending sister chromatids leads to changes in the genetic information = a mutation. • Cells try to avoid generating mutations. • A checkpoint is a stage in the cell cycle where the cycle can be stopped if there is a problem. • If the problem is fixed  resume the cycle. • If the problem can’t be fixed  cell death. • The cell death process is called apoptosis (= programmed cell death, cell suicide). apo = from, away from (Greek) ptosis = falling or dropped (Greek) Cell Division - Regulation Checkpoints • Different things are checked at different checkpoints. • But checks for DNA damage are always part of the picture. • M Checkpoint = the “spindle checkpoint”; -checks that all the sister chromatids are correctly attached to the spindle microtubules -the cycle will not proceed until the kinetochores of each pair of sister chromatids are anchored to the spindle fibers. • There are various cellular DNA repair systems. • But not all DNA damage can be repaired. Cell Division - Apoptosis • Apoptosis is programmed cell death. • Tightly-regulated (and much studied) defined biochemical process. • Occurs in various situations: 1) cells with DNA damage that cannot be repaired (if it can’t be fixed, kill it) 2) as part of normal developmental processes to get rid of unwanted cells (e.g. between the fingers of a developing hand) Do not memorize this diagram. https://www.genome.gov/sites/default/files/tg/en/illustration/apoptosis.jpg Cell Division – Checkpoints & Apoptosis Cell reaches a checkpoint Pass the checkpoint Fail the checkpoint Fix the problem Cannot fix the problem Continue through the cell cycle Continue through the cell cycle Apoptosis (cell death) Cell Division Cancer and cell cycle regulation • The various types of cancer are often partly a cell cycle dis-regulation disease. The importance of “model organisms”: • Certain organisms are well-suited to investigate certain types of questions. • A lot of cell cycle regulation research has been done with fission yeast (Schizosaccharomyces pombe) and baker’s yeast (Saccharomyces cerevisiae). • Not because the yeast are inherently fascinating (actually, there are fascinating), but because they are eukaryotes and the cell cycle is regulated in yeast in ways that are similar to other eukaryotes, including humans. fission yeast By David O Morgan - The Cell Cycle. Principles of Control., Attribution, https://commons.wikimedia.org/w/index.php?curid=8627875 Cell Division Summary • Mitotic cell division results in conservation of genetic information. • Chromosomes with sister chromatids is a prerequisite for cell division. • The sister chromatids are identical (exactly the same info). • Individual chromosomes line up at the centre of the cell during mitosis;  contraction of the spindle pulls sister chromatids to opposite ends of the cell • Cell division is part of the cell cycle, and the cell cycle is tightly regulated. • Multicellular organisms “grow” via mitotic cell division. • There are sometimes errors in DNA replication; -DNA repair mechanisms exist -if the DNA cannot be repaired  apoptosis Next Up: • Meiosis, or meiotic cell division. • Important differences from mitotic cell division: 1) two rounds of cell division 2) homologous pairs of chromosomes line up at the centre of cell in Meiosis I 3) contraction of the spindle in Meiosis I leads to homologous chromosomes being pulled in opposite directions (not sister chromatids)

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