UM1011 Cell Cycle 2024 Student PDF

Dr Katja Vogt Inductory video A video of cells deviding (TC) @katjetz [email protected] [email protected] BSc Medical Sciences  Dr Katja Vogt The Cell cycle and Apoptosis @katjetz School of Medicine [email protected] KVogt@uclan...

Dr Katja Vogt Inductory video A video of cells deviding (TC) @katjetz [email protected] [email protected] BSc Medical Sciences  Dr Katja Vogt The Cell cycle and Apoptosis @katjetz School of Medicine [email protected] [email protected] BSc Medical Sciences 2  Dr Katja Vogt Prelim slide  Dr Katja Vogt Today we are going to … … explain the cell cycle, mitosis and cytokinesis … derive meiosis as specific form of mitosis … highlight how is the cell cycle regulated … identify the importance of the metaphase for cytogenetics … discuss apoptosis as consequence of cell signalling and cell cycle failure Twitter: @katjetz E-mail: [email protected] [email protected] BSc Medical Sciences  Dr Katja Vogt Cellular Reproduction: Multiplication by Division Process in 4 phases 1. Cell growth (G1 phase) 3. Preparation for division (G2 phase) 2. DNA replication (S phase) 4. Cell divides and forms 2 cells (M phase) Cell Growth DNA replication Preparation Cell division Twitter: @katjetz E-mail: [email protected] [email protected] 6 BSc Medical Sciences  Dr Katja Vogt Definitions Twitter: @katjetz E-mail: [email protected] [email protected] 7 BSc Medical Sciences  Dr Katja Vogt Cell cycle  Dr Katja Vogt Cell cycle G1 Phase: rapid cell growth metabolic active duplication of cell organelle and cytosolic components start of centrioles replication Cell can exit G1 and go into G0 (differentiate, apoptosis)  Dr Katja Vogt Cell cycle. G1 Phase: rapid cell growth metabolic active duplication of cell organelle and cytosolic components start of centrioles replication S Phase: DNA replication and Cell can exit G1 and go into G0 further growth (differentiate, apoptosis)  Dr Katja Vogt Cell cycle G2 phase: cell growth continues G1 Phase: preparation for cell division rapid cell growth enzymes and other metabolic active proteins are duplication of cell synthesised organelle and cytosolic components replication of centrioles start of centrioles completed replication S Phase: DNA replication and Cell can exit G1 and go into G0 (differentiate, apoptosis) further growth  Dr Katja Vogt Cell cycle G2 phase: cell growth continues G1 Phase: preparation for cell division rapid cell growth enzymes and other metabolic active proteins are duplication of cell synthesised organelle and cytosolic components replication of centrioles start of centrioles completed replication S Phase: DNA replication and Cell can exit G1 and go into G0 (differentiate, apoptosis) further growth  Dr Katja Vogt Chromatin packaging Twitter: @katjetz E-mail: [email protected] [email protected] 13 BSc Medical Sciences  Dr Katja Vogt DNA packaging Twitter: @katjetz E-mail: [email protected] [email protected] 14 BSc Medical Sciences  Dr Katja Vogt Our DNA is packed in chromosomes Twitter: @katjetz E-mail: [email protected] [email protected] 15 BSc Medical Sciences  Dr Katja Vogt Histones Quite small, but abundant proteins Rich in arginine and lysine Subject to protein modifications Important for structure and regulation Twitter: @katjetz E-mail: [email protected] [email protected] BSc Medical Sciences  Dr Katja Vogt Chromatin Twitter: @katjetz E-mail: [email protected] [email protected] BSc Medical Sciences  Dr Katja Vogt Nucleosome Twitter: @katjetz E-mail: [email protected] [email protected] BSc Medical Sciences  Dr Katja Vogt Chromosome Twitter: @katjetz E-mail: [email protected] [email protected] BSc Medical Sciences  Dr Katja Vogt Chromatid Twitter: @katjetz E-mail: [email protected] [email protected] BSc Medical Sciences  Dr Katja Vogt Centromere Twitter: @katjetz E-mail: [email protected] [email protected] BSc Medical Sciences  Dr Katja Vogt Centrosome Twitter: @katjetz E-mail: [email protected] [email protected] BSc Medical Sciences  Dr Katja Vogt Spindle Twitter: @katjetz E-mail: [email protected] [email protected] BSc Medical Sciences  Dr Katja Vogt Kinetochore Twitter: @katjetz E-mail: [email protected] [email protected] BSc Medical Sciences  Dr Katja Vogt Nomenclature Chromatin: complex of DNA and histones that makes up the basic material of eukaryotic chromosomes Nucleosome: Structure in chromatin composed of short DNA wrapped around an octameric core of histone proteins Chromosome: structure composed of condensed DNA and associated proteins, which carries the genetic information Chromatid: one of the copy of a chromosome present after DNA replication Centromere: holds together 2 sister chromatids Centrosome: organelle which organises the microtubule cytoskeleton Spindle: structures formed by the microtubules, stretching between opposite poles of the cell and which guides the movement of the chromosomes Kinetochore: protein complex that binds to a region at the centromere of a chromosome to which spindle microtubule attach Definitions adapted from Henderson’s Dictionary of biology 13th edition Twitter: @katjetz E-mail: [email protected] [email protected] BSc Medical Sciences  Dr Katja Vogt Mitosis Twitter: @katjetz E-mail: [email protected] [email protected] BSc Medical Sciences  Dr Katja Vogt Prophase Microtubule DNA  Dr Katja Vogt Prometaphase Microtubule DNA  Dr Katja Vogt Metaphase Microtubule DNA  Dr Katja Vogt Anaphase Microtubule DNA  Dr Katja Vogt Telophase Microtubule DNA  Dr Katja Vogt Cytokinesis Microtubule DNA  Dr Katja Vogt Mitotic spindle  Dr Katja Vogt Motor proteins involved Twitter: @katjetz E-mail: [email protected] [email protected] BSc Medical Sciences  Dr Katja Vogt Meiosis Meiosis is special type of cell division Occurs only in the cells that will form sperm and egg cells Results in half the usual chromosomes (one from each pair) DNA replication Twitter: @katjetz E-mail: [email protected] [email protected] BSc Medical Sciences  Dr Katja Vogt Meiosis Twitter: @katjetz E-mail: [email protected] [email protected] 36 BSc Medical Sciences  Dr Katja Vogt Break time Twitter: @katjetz E-mail: [email protected] [email protected] BSc Medical Sciences  Dr Katja Vogt Checkpoints Twitter: @katjetz E-mail: [email protected] [email protected] BSc Medical Sciences  Are all chromosomes Is all DNA replicated? attached to the spindle? G2/M Checkpoint Is the environment favourable? M TRIGGER ANAPHASE AND PROCEED TO CYTOKINESIS ENTER MITOSIS G2 G1 G0 Interphase ENTER CELL CYCLE AND PROCEED TO S PHASE Checkpoints S G1/S Checkpoint Is the environment favourable?  Dr Katja Vogt Checkpoints Responds to information received back from the cells Triggers events of the cell cycle and ensures their timing and coordination Binary biochemical switches (on/off) Launch events in a complete and irreversible fashion  Dr Katja Vogt Checkpoints - the cell-cycle control system Robust and reliable with backup mechanisms Highly adaptable Two key component system Cyclins - cycle throughout the cell cycle :) Twitter: @katjetz E-mail: [email protected] [email protected] BSc Medical Sciences  Dr Katja Vogt Cell cycle checkpoint details Chromosomes Favourable DNA damage Unreplicated DNA unattached to extracellular the spindle environment G1/S G2/M M Checkpoint Checkpoint Checkpoint Point of no return G1 is entered when external Check DNA quality Check of Check stimuli are right Ascertain external chromosomes chromosomes Start the process environment Ascertain DNA are correctly of cell division attached to replication spindle Apoptosis  Dr Katja Vogt There is some more… Twitter: @katjetz E-mail: [email protected]  Dr Katja Vogt Cytogenetics Chromosome Banding Also called G-Band or Giemsa bands dark regions are rich in A and T Twitter: @katjetz E-mail: [email protected] [email protected] BSc Medical Sciences  Dr Katja Vogt Typical metaphase spread  Dr Katja Vogt Please stand up if you identify with this Karyotype Twitter: @katjetz E-mail: [email protected] [email protected] BSc Medical Sciences  Dr Katja Vogt Please stand up if you identify with this Karyotype Do you identify with this karyotype Twitter: @katjetz E-mail: [email protected] [email protected] BSc Medical Sciences  Dr Katja Vogt Clinical relevance of metaphase in cytogenetics Karyotyping of chromosomes in metaphase Diagnostic tool: extra chromosomes missing chromosomes missing portions of a chromosome extra portions of a chromosome Male Female portions that have broken off of one chromosome and reattached to another  Dr Katja Vogt Karyotype duplication  Dr Katja Vogt Karyotype translocation  Dr Katja Vogt Karyotype deletion  Dr Katja Vogt Apoptosis Twitter: @katjetz E-mail: [email protected]  Dr Katja Vogt Developing mouse paw Apoptosis Apoptotic cells Normal and essential event during esp. development and within the immune system Fast process, superficially resemble mitotic cells Average adult human looses between 50-70 million cells due to apoptosis Does not lead to lysis of cells Avoids damage to neighbouring tissue Pancreas Cardiac (infact)  Dr Katja Vogt Apoptotic cell characteristics 1. Membrane blebbing 2. Cell shrinkage, dense cytoplasm 3. Nuclear fragmentation 4. Chromatin condensation 5. chromosomal DNA fragmentation 6. mRNA degradation 7. Separation of cell fragments into apoptotic bodies 8. Organelle integrity and membranes still intact Twitter: @katjetz E-mail: [email protected] [email protected] BSc Medical Sciences  Dr Katja Vogt Apoptosis in the clinical context Some conditions feature insufficient apoptosis whereas others feature excessive apoptosis. Hands up when excessive apoptosis! Cancer AIDS Ischemia Autoimmune lymphoproliferative syndrome Neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, Amyotrophic Lateral Sclerosis.  Dr Katja Vogt Signal transduction in apoptosis Proteolytic cascade that is mediated by caspases Irreversible process Two main pathways Triggered by cell surface Triggered by chemicals, death receptors radiations, loss of attachment to extracellular matrix or growth factor withdrawal Depends on mitochondria Twitter: @katjetz E-mail: [email protected] [email protected] BSc Medical Sciences  Dr Katja Vogt Caspase activation Caspase: protease with cysteine, that cleave their target at specific aspartic acid Initiator and executioner caspases  Dr Katja Vogt FASL FAS FADD Pro caspase8 Active caspase8 Pro caspase3 Active Twitter: @katjetz caspase3 E-mail: [email protected] [email protected] Substrates BSc Medical Sciences  Dr Katja Vogt Inactive anti-apoptotic (eg.Bcl2) Aggregated active pro- apoptotic effector Active (eg.Bax/Bak) proapoptotic BH3- only protein (eg. Bad/Bim) Twitter: @katjetz E-mail: [email protected] [email protected] BSc Medical Sciences  Dr Katja Vogt Apoptotic Stimulus Bax Caspase9 Cytochrome C Apoptosome Pro caspase3 Active Twitter: @katjetz caspase3 E-mail: [email protected] [email protected] Substrates BSc Medical Sciences  Dr Katja Vogt FASL Apoptotic FAS FADD Stimulus Pro Bax caspase8 Caspase9 Cytochrome C Active caspase8 Apoptosome Pro caspase3 Active Twitter: @katjetz caspase3 E-mail: [email protected] [email protected] Substrates BSc Medical Sciences  Dr Katja Vogt FASL Apoptotic FAS FADD Stimulus Pro Bax caspase8 Caspase9 Cytochrome C Active caspase8 Apoptosome Pro caspase3 Active Twitter: @katjetz caspase3 E-mail: [email protected] [email protected] Substrates BSc Medical Sciences  Dr Katja Vogt Example: PI3Kinase signalling in apoptosis Twitter: @katjetz E-mail: [email protected] [email protected] 63 BSc Medical Sciences  Dr Katja Vogt Apoptosis - summary Twitter: @katjetz E-mail: [email protected] Any Questions?  Dr Katja Vogt Reading list “Essential Cell Biology”- Alberts, B. et al. 2014 17 (cell cycle) Chapter 3. The Nucleus & Cell Cycle. In: Paulsen DF. eds. Histology & Cell Biology: Examination & Board Review, 5e New York, NY: McGraw-Hill; 2010. http://accessmedicine.mhmedical.com/content.aspx?bookid=563&sectionid=42045296. Clinical Cytogenetics. In: Schaefer G, Thompson, Jr. JN. eds. Medical Genetics: An Integrated Approach New York, NY: McGraw-Hill;. http://accessmedicine.mhmedical.com/content.aspx?bookid=2247&sectionid=173744189. Meisenberg, Gerhard, PhD; Simmons, William H., PhD; Principles of Medical Biochemistry, Chapter 19, 316-340 Twitter: @katjetz E-mail: [email protected] [email protected] BSc Medical Sciences  Dr Katja Vogt MBBS Learning outcomes Describe key examples of signal transduction pathways in apoptosis Define the cell cycle, mitosis and cytokinesis Recognise the clinical relevance of metaphase in cytogenetics Twitter: @katjetz E-mail: [email protected] [email protected] BSc Medical Sciences