UM1010 Cell Cycle 2023 Pre-Lecture Notes PDF

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

Dr Katja Vogt Inductory video A video of cells deviding (TC) @katjetz [email protected] BSc Medical Sciences  Dr Katja Vogt The Cell cycle @katjetz [email protected] BSc School of Medicine Medical Sciences 2  Dr Katja Vogt Prelim slide  Dr Katja Vogt The Cell cycle Learning objectives Explain the cell cycle, mitosis and cytokinesis Discuss the mitotic process Derive meiosis as specific form of mitosis Recognise how is the cell cycle regulated Identify the importance of the metaphase for cytogenetics @katjetz [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] 6 BSc Medical Sciences  Dr Katja Vogt Definitions Twitter: @katjetz E-mail: [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] 13 BSc Medical Sciences  Dr Katja Vogt DNA packaging Twitter: @katjetz E-mail: [email protected] 14 BSc Medical Sciences  Dr Katja Vogt Our DNA is packed in chromosomes Twitter: @katjetz E-mail: [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] BSc Medical Sciences  Dr Katja Vogt Complex of DNA and histones that makes up the basic material of eukaryotic chromosomes Twitter: @katjetz E-mail: [email protected] BSc Medical Sciences  Dr Katja Vogt Structure in chromatin composed of short DNA wrapped around an octameric core of histone proteins Twitter: @katjetz E-mail: [email protected] BSc Medical Sciences  Dr Katja Vogt Structure composed of condensed DNA and associated proteins, which carries the genetic information Twitter: @katjetz E-mail: [email protected] BSc Medical Sciences  Dr Katja Vogt One of the copy of a chromosome present after DNA replication Twitter: @katjetz E-mail: [email protected] BSc Medical Sciences  Dr Katja Vogt Holds together 2 sister chromatids Twitter: @katjetz E-mail: [email protected] BSc Medical Sciences  Dr Katja Vogt Organelle which organises the microtubule cytoskeleton Twitter: @katjetz E-mail: [email protected] BSc Medical Sciences  Dr Katja Vogt Structures formed by the microtubules, stretching between opposite poles of the cell and which guides the movement of the chromosomes Twitter: @katjetz E-mail: [email protected] BSc Medical Sciences  Dr Katja Vogt Protein complex that binds to a region at the centromere of a chromosome to which spindle microtubule attach Twitter: @katjetz E-mail: [email protected] BSc Medical Sciences  Dr Katja Vogt Mitosis Twitter: @katjetz E-mail: [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] 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] BSc Medical Sciences  Dr Katja Vogt Meiosis Twitter: @katjetz E-mail: [email protected] 35 BSc Medical Sciences  Dr Katja Vogt End of part 1 Cell cycle End of Part 1 You should be able to… Explain the cell cycle, mitosis and cytokinesis Recognise and highlight the characterises of the different stages within the cell cycle Discuss the mitotic process Twitter: @katjetz E-mail: [email protected] BSc Medical Sciences  Dr Katja Vogt Break time Twitter: @katjetz E-mail: [email protected] BSc Medical Sciences  Dr Katja Vogt Checkpoints Twitter: @katjetz E-mail: [email protected] BSc Medical Sciences  Are all chromosomes Is all DNA replicated? t attached to the spindle? poin G2/M Checkpoint heck Is the environment favourable? MC 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] BSc Medical Sciences  Dr Katja Vogt G1/S Checkpoint Mitogens push cells through the G1/S checkpoint At the G 1 checkpoint, however, both pRb and E2F become phosphorylated by the kinase complexes of cyclins D and E Phosphorylated pRb falls off the transcription factor, and the genes can be transcribed. Mitogens Twitter: @katjetz E-mail: [email protected] BSc Medical Sciences  Dr Katja Vogt DNA Damage Checkpoints Responses to DNA damage are coordinated by the nuclear phosphoprotein p53 p53 is a transcription factor that drives the expression of genes for growth arrest, DNA repair, senescence and apoptosis It is present in low concentrations at all times Damage-activated protein kinases that Sensors phosphorylate p53 and hence activate it Other p53 activating stimuli include: oxidative stress, hypoxia, inhibition of transcription or translation, and osmotic stress Twitter: @katjetz E-mail: [email protected] BSc Medical Sciences  Dr Katja Vogt M checkpoint (spindle assembly checkpoint)  Dr Katja Vogt M checkpoint (spindle assembly checkpoint) Prior to entry of anaphase Senses the completion of microtubule binding to kinetochores at metaphase Its default setting is “on” as cells enter mitosis. It is silenced only when every chromosome is properly attached to the spindle Unattached kinetochore sends an inhibitory signal APC/C (anaphase-promoting complex/cyclosome) bound to substrate recognition factor Cdc20 Key APC/C substrates are proteins that must be degraded for the cell to move from metaphase to anaphase Kinetochores without microtubules assemble the mitotic checkpoint complex (MCC), the inhibitor that inactivates APC/C Twitter: @katjetz E-mail: [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  APC/C: t poin G2 /M Checkpoint Cyclin B Summary heck MC Cdk1 M Cdki: p15, p16, p19, G2 p21, p27, p57 G1 G0 Interphase Cyclin D Cdk4/6 S Rb Cyclin A G1/S Checkpoint Cdk2 Cyclin E Transcription of subsequent Cyclins Cdk2 Any Questions?  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] 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] 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] BSc Medical Sciences  Dr Katja Vogt Clinical relevance of metaphase in cytogenetics Karyotyping of chromosomes in metaphase Diagnostic tool: extra chromosomes Why d oes it missing chromosomes n eed t o be d missing portions of a chromosome one in Me taphas extra portions of a chromosome ? e Male Female portions that have broken off of one chromosome and reattached to another n o rmal? e oso mes ar hrom H ow many c  Dr Katja Vogt Karyotype duplication  Dr Katja Vogt Karyotype translocation  Dr Katja Vogt Karyotype deletion  Dr Katja Vogt Cell cycle (LOs) Learning outcomes: Define the cell cycle, mitosis and cytokinesis Recognise the clinical relevance of metaphase in cytogenetics Twitter: @katjetz E-mail: [email protected]  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] BSc Medical Sciences