HLTH1005-Week 08_Mitosis-and-the-Cell-Cycle (Student Copy).pdf

Mitosis and the Cell Cycle H LT H 1 0 0 5 – C e l l u l a r B i o l o g y & G e n e t i c s Week8 Dr. Hassan Choucair School of Health Sciences Sydney | University of Notre Dame Australia [email protected] CRICOS PROVIDER CODE...

Mitosis and the Cell Cycle H LT H 1 0 0 5 – C e l l u l a r B i o l o g y & G e n e t i c s Week8 Dr. Hassan Choucair School of Health Sciences Sydney | University of Notre Dame Australia [email protected] CRICOS PROVIDER CODE 01032F notredame.edu.au ACKNOWLEDGEMENT OF COUNTRY The University of Notre Dame Australia is proud to acknowledge the traditional owners and custodians of this land upon which our University sits. The University acknowledges that the Fremantle Campus is located on Wadjuk Country, the Broome Campus on Yawuru Country and the Sydney Campus on Cadigal Country.  Lecture Objectives Distinguish between prokaryotic and eukaryotic cell division Understand the key phases of the cell cycle: G0/1, S, G2, and M/C Explain the roles of cyclins and cyclin-dependent kinases (CDKs) in regulating the cell cycle Describe the function and significance of cell cycle checkpoints, including G1/S and G2/M, and their regulatory mechanisms Analyse the role of tumour suppressor network, particularly p21 and p53, in controlling the cell cycle Identify and describe the phases of mitosis: Prophase, Prometaphase, Metaphase, Anaphase, and Telophase Differentiate between mitosis and cytokinesis Investigate the implications of cell cycle errors and their association with diseases like cancer Explore research techniques for studying mitosis and the cell cycle CRICOS PROVIDER CODE 01032F notredame.edu.au  Cell division and the cell cycle Critical for growth, development, and tissue repair In prokaryotes, a single cell-division cycle is to ensure its survival In eukaryotic cells, the cell cycle is divided into two main stages: Interphase M phase (includes cytokinesis) Involves two major types: – Mitosis – Meiosis (Week 12) Controlled by checkpoints to ensure accuracy and prevent errors CRICOS PROVIDER CODE 01032F notredame.edu.au  Prokaryotic cell division Bacterial cell cycle divided into B, C, and D periods B period: time between cell birth and initiation of DNA replication C period: DNA replication begins at the origin (oriC) and proceeds bidirectionally → halving replication time D period (binary fission): time between end of replication and cell division Chromosome remains condensed as a nucleoid during replication Nat Rev Microbiol. 2009 Nov; 7(11): 822–827 CRICOS PROVIDER CODE 01032F notredame.edu.au Cell cycle in eukaryotes Time in vertebrate cells CRICOS PROVIDER CODE 01032F notredame.edu.au  Cell cycle in eukaryotes Consists of four distinct phases: G1, S, G2, and M Concludes in the formation of two identical daughter cells Activation of each phase depends on the proper completion of the previous phase Cells in a state of quiescence are in G0 phase (resting phase) – Temporarily or reversibly stopped dividing CRICOS PROVIDER CODE 01032F notredame.edu.au  G0 (quiescent phase) Resting phase where the cell has left the cell cycle and stopped dividing Fully differentiated and non-proliferating cells frequently enter G0, and may remain quiescent indefinitely: – Red blood cells – Mature neurons – Cardiac and skeletal muscle cells Most epithelial cells do not enter G0 and continue dividing throughout an organism's life – Hepatocytes, renal, and gastric epithelial cells enter the G0 phase semi- permanently – Only re-enter the cell cycle if needed for repair or regeneration CRICOS PROVIDER CODE 01032F notredame.edu.au  Quiescence vs. senescence Both states involve cells not actively dividing Quiescence is reversible and cells are metabolically active Senescence is irreversible, cells permanently exit the cell cycle due to DNA damage or stress, and may contribute to aging and tissue dysfunction CRICOS PROVIDER CODE 01032F notredame.edu.au  Interphase: G1 First gap phase within interphase, from the end of the previous M phase until DNA synthesis begins “Growth phase”, with high biosynthetic activity resuming after M phase – Cell increases proteins, organelles, and overall size Restriction point: cell continues to S phase, enter G0 for differentiation, or become arrested in G1 CRICOS PROVIDER CODE 01032F Yeast cell cycle and growth is dependent on cell size notredame.edu.au  Interphase: S (“synthesis”) DNA synthesis results in the replication of all chromosomes Each chromosome consists of two sister chromatids DNA content doubles but chromosome number remain unchanged RNA transcription and protein synthesis are minimal, except for histone production Most histone synthesis occurs Note: Chromosomes are depicted as condensed, during S phase to support but they only condense during mitosis new chromatin formation (Week 9) CRICOS PROVIDER CODE 01032F notredame.edu.au Week 9 lecture prelude... CRICOS PROVIDER CODE 01032F notredame.edu.au  Interphase: G2 Second gap phase within interphase, follows DNA replication Involves protein synthesis and rapid cell growth in preparation for mitosis Microtubules begin to reorganise into centrosomes and form the “mitotic spindle” in anticipation of chromosome separation The G2 checkpoint ensures there is no DNA damage before proceeding to mitosis Centrosome duplicates during S phase to ensure that two CRICOS PROVIDER CODE 01032F centrosomes are present for spindle formation notredame.edu.au  Regulation of eukaryotic cell cycle Key regulators: – Cyclins – Cyclin-dependent kinases (CDKs) – Inhibitors Checkpoints are critical control points that assess cell readiness to progress through different phases CRICOS PROVIDER CODE 01032F notredame.edu.au Cyclins and CDKs CDKs are enzymes that can modify protein substrates involved in cell cycle progression Cyclin-CDK complexes phosphorylate their substrates by transferring phosphate groups from ATP to specific amino acids on the substrates CDKs are inactive without a cyclin partner CRICOS PROVIDER CODE 01032F notredame.edu.au Cyclins and CDKs Vertebrates have at least 20 CDKs, with CDK1, CDK2, CDK4, and CDK6 being key for cell cycle regulation Around 29 cyclins in vertebrates, classified by their role in different cell cycle phases. Key cyclins: A, B, D, and E CRICOS PROVIDER CODE 01032F notredame.edu.au CDK-cyclin activation timeline G1 phase: Cyclin D activates CDK4/CDK6 G1/S transition: Cyclin E activates CDK2 S phase: Cyclin A activates CDK2 for DNA replication G2/M transition: Cyclin A activates CDK1 M phase: Cyclin B activates CDK1 to drive mitosis completion CRICOS PROVIDER CODE 01032F notredame.edu.au Cell cycle checkpoints G1 checkpoint Assesses cell size, nutrient availability, and DNA integrity before entering S phase G2 checkpoint Ensures that DNA replication is complete and checks for DNA damage before proceeding to mitosis Metaphase (mitosis) checkpoint Verifies that chromosomes are attached to the spindle apparatus before anaphase begins CRICOS PROVIDER CODE 01032F notredame.edu.au  Cell cycle inhibitor: p21 Triggered by DNA damage p21 halts the cell cycle in G1 by inactivating cyclin-CDK complexes – Allows time for repair or triggers cell death if damage is irreparable p53-related Activated by the tumour cell death suppressor protein p53 Activates complex to inhibit Mutations or loss of p53 can lead transcription to reduced p21 activation, resulting in unchecked cell cycle progression → tumorigenesis CRICOS PROVIDER CODE 01032F notredame.edu.au  Mitosis: M phase Eukaryotic cell divides its chromosomes into two identical sets, each in a separate nucleus Chromosomes condense and attach to microtubules that pull sister chromatids to opposite sides of the cell Varies between species: – In fungi and yeast, mitosis is "closed," with chromosome division occurring inside an intact nucleus CRICOS PROVIDER CODE 01032F notredame.edu.au  Mitosis: M phase Four main phases sequentially: Prophase – Prometaphase Metaphase Anaphase Telophase CRICOS PROVIDER CODE 01032F notredame.edu.au Mitosis: Prophase Chromosomes condense The mitotic spindle (made of microtubules, “asters”), begins to form from centrosomes Centrosomes move to opposite poles of the cell The nuclear envelope starts to break down, allowing spindle fibres to attach to chromosomes Prophase Prometaphase Interphase CRICOS PROVIDER CODE 01032F notredame.edu.au Mitosis: Prometaphase Chromosomes begin to move toward the cell's equatorial plane (metaphase plate) in preparation for alignment The ER and Golgi fragment and disperse Mitochondria, chloroplasts, lysosomes, and peroxisomes remain intact and evenly distributed between daughter cells CRICOS PROVIDER CODE 01032F notredame.edu.au Mitosis: Metaphase Chromosomes align at the metaphase plate Sister chromatids are aligned for separation through tension from the spindle fibres The metaphase checkpoint (spindle assembly checkpoint) ensures that all chromosomes are properly attached to the spindle before proceeding to anaphase CRICOS PROVIDER CODE 01032F notredame.edu.au Mitosis: Anaphase Sister chromatids are separated as centromeres split Two parts – Anaphase A: chromosomes pulled to opposite poles – Anaphase B: spindle poles move farther apart The cell elongates → sliding of microtubules to each other CRICOS PROVIDER CODE 01032F notredame.edu.au Mitosis: Telophase Chromosomes de-condense and nuclear envelopes reform around each nucleus Nucleoli reappear, and the mitotic spindle disassembles Cyclin levels drop, inhibiting CDKs The cell prepares for cytokinesis CRICOS PROVIDER CODE 01032F notredame.edu.au Cytokinesis Divides the cytoplasm, organelles, and cell membrane into two daughter cells with equal components In animal cells, involves the formation cleavage furrow that separates the cytoplasm Mitosis and cytokinesis together complete the cell cycle CRICOS PROVIDER CODE 01032F notredame.edu.au Mitosis and cytokinesis in plants Cell cycle is generally conserved between animals and plants Plant cell differences During cytokinesis, a cell plate forms a new cell wall Lack centrosomes and use other structures to form spindles Have rigid cell walls, influencing cytokinesis mechanics CRICOS PROVIDER CODE 01032F notredame.edu.au Summary CRICOS PROVIDER CODE 01032F OpenStax, Biology. OpenStax CNX. May 27, 2016notredame.edu.au http://cnx.org/contents/[email protected]:Vbi92lHB@9/The-Cell-Cycle  Cell cycle disorders: Cancer In normal cell cycle, BRCA1 and BRCA2 repair DNA double-strand breaks during cell division Mutations increase breast, ovarian, prostate, and pancreatic cancer risk BRCA1 and BRCA2 abnormalities occur in about 1 in 400 Australians – 1 in 40 among Ashkenazi Jewish communities CRICOS PROVIDER CODE 01032F notredame.edu.au  Research techniques to study cell cycle Flow cytometry for cell cycle Technique for analysing cell cycle phases and progression Microscopy for mitosis Provide detailed insights into mitotic progression and abnormalities CRICOS PROVIDER CODE 01032F notredame.edu.au  Recommended Readings Ladiges et al. (2014). Biology: An Lecture Summary Australian focus. Part 1, Chapter 8. Pollard et al. (2023). Cell biology. Section X (Chapter’s 41–46). Prokaryotic cell division involves binary fission, while eukaryotic cells undergo mitosis and cytokinesis Key cell cycle phases: G0/1 (growth/rest), S (DNA replication), G2 (preparation for mitosis), and M/C (mitosis and cytokinesis) Cyclins and CDKs regulate the cell cycle by controlling transitions between phases Cell cycle checkpoints, such as G1/S and G2/M, monitor and regulate progression to ensure accurate division  Recommended Readings Ladiges et al. (2014). Biology: An Lecture Summary Australian focus. Part 1, Chapter 8. Pollard et al. (2023). Cell biology. Section X (Chapter’s 41–46). Tumour suppressor p53 plays crucial role in cell cycle control, with p21 inhibiting CDKs and p53 responding to DNA damage Mitosis phases: Prophase, Prometaphase, Metaphase, Anaphase, and Telophase Mitosis involves chromosome separation, while cytokinesis divides the cytoplasm and organelles into two cells Cell cycle errors can lead to diseases like cancer, highlighting the importance of accurate cell division Techniques for studying cell cycle and mitosis include microscopy (e.g., live-cell imaging) and molecular methods (e.g., flow cytometry)  THANK YOU! QUESTIONS? Post to the Discussion Board J