BO101 Cell Biology Lecture 3 Cell Cycle & Mitosis 2024 PDF

Cell Cycle and Mitosis BO101 - Cell Biology - Lecture 3 Dr Andrew Flaus, Biochemistry Omnis cellula e cellula Every cell from a cell “The ability of organisms to reproduce their own kind is the one characteristic that best distinguishes living things from non-living matter” Virchow, 1858 Cell divi...

Cell Cycle and Mitosis BO101 - Cell Biology - Lecture 3 Dr Andrew Flaus, Biochemistry Omnis cellula e cellula Every cell from a cell “The ability of organisms to reproduce their own kind is the one characteristic that best distinguishes living things from non-living matter” Virchow, 1858 Cell division ๏ Cell division results in identical daughters ‣ Transfer information is the basis of genetics ๏ Chromosomes ‣ Organise DNA of genome ‣ Provide vehicle for moving DNA during cell division ‣ Must be replicated before cell division Campbell ed 9 g 12.1 fi Cell cycle has four phases ๏ G1 ‣ Gap 1 ‣ General function and metabolism ๏ S ‣ Synthesis ‣ Replication of DNA ๏ G2 ‣ Gap 2 ‣ Wait for chromosome segregation ๏ M ‣ Mitosis phase ‣ Replicated chromosomes segregate Campbell g 12.6 fi Phases are grouped in 2 blocks ๏ Interphase ‣ G1, S, G2 phases ‣ Chromosomes decondensed ๏ Mitotic phase ‣ M phase ‣ Chromosomes condensed Campbell g 12.6 fi Mitosis has 5 stages ๏ Prophase ๏ Prometaphase ๏ Metaphase ๏ Anaphase ๏ Telophase & cytokinesis Campbell g 12.6 fi Mechanism of mitosis BioFlix 12_07 Mitosis Stages of mitosis G2 Prophase Prometaphase Metaphase Anaphase Telophase & (interphase) Cytokinesis Campbell g 12.7 fi (S of interphase) ๏ S = Synthesis (of DNA) ‣ Replication = duplication of entire genome ๏ Each copy becomes a sister chromatid ‣ Sister chromatids remain associated until mitosis Campbell g 12.5 fi (G2 of interphase) ๏ Preparation for mitosis ๏ Nuclear envelope in place ๏ Two centrosomes formed ๏ Chromosomes are diffuse ‣ Not yet condensed Campbell g 12.7 fi Prophase ๏ Mitotic spindle forms as centrosomes separate ๏ Chromatin bres condensing ๏ Sister chromatids visible Campbell g 12.7 fi fi Prometaphase ๏ Nuclear envelope fragmented ๏ Microtubules enter nuclear area ๏ Fully condensed chromosomes become visible ‣ Chromatids ‣ Centromeres Campbell g 12.7 fi Metaphase ๏ Centrosomes at opposite poles ๏ Microtubules connect centrosomes to kinetochores ๏ Chromosomes aligned on metaphase plate Campbell g 12.7 fi Mitotic spindle pulls chromosomes ๏ Centrosome ‣ Organising centres at cell poles ๏ Aster ‣ Radiating microtubules that position centrosomes ๏ Microtubules ‣ Protein ‘ropes’ ๏ Kinetochore ‣ Attachment linking microtubules to centromere Campbell g 12.8 fi Anaphase ๏ Cell elongates as non-kinetochore microtubules lengthen ๏ Sister chromatids pulled apart to opposite poles Campbell g 12.7 fi Telophase & Cytokinesis ๏ Telophase ‣ Nuclear envelopes reappear ‣ Chromosomes decondense ๏ Cytokinesis Campbell g 12.7 fi Telophase & Cytokinesis ๏ Telophase ‣ Nuclear envelopes reappear ‣ Chromosomes decondense ๏ Cytokinesis ‣ Cytoplasms separate ‣ Cleavage furrow Ring of actin laments with myosin motor acts like drawstring Campbell g 12.7 fi fi BioFlix 12_07 Mitosis Summary of stages of mitosis (S phase) Replication of genome (G2 phase) Preparation for mitosis Prophase Chromosome condensation Attachment of spindles Metaphase Alignment along plate Anaphase Separation of chromosomes Chromosome decondensation Telophase Reforming of nuclear envelope Cytokinesis Cytoplasm divides forming daughter cells Identical copies of genetic information Mitosis segregated to equivalent daughter cells Binary ssion ๏ Cell division mechanism ‣ Alternative to mitosis ‣ Chromosomes separate as they replicate ‣ No pulling by microtubules ๏ Asexual process used by ‣ Bacteria ‣ Asexual single-cell eukaryotes Campbell g 12.12 fi fi Cell cycle regulation Molecular cycle controls cell cycle ๏ Cell cycle control ‣ Molecular cycle runs in parallel to control the cell cycle ‣ “Molecular clock” Campbell g 12.15 fi Cell cycle checkpoints ๏ Cell cycle control ‣ Molecular cycle runs in parallel to control the cell cycle ๏ Checkpoints ‣ Stop points in cycle Ensure cycle does not progress until preceding steps completed ‣ Three major checkpoints: G1-to-S G2-to-M Intra M ‣ Deregulation in cancer Campbell g 12.15 fi G0 to switch out of cell cycle ๏ Cell cycle control ‣ Molecular cycle runs in parallel to control the cell cycle ๏ Checkpoints ‣ Stop points in cycle ‣ Three major checkpoints ๏ G1 checkpoint block ‣ Cells can go to G0 ‣ Non-dividing state Campbell g 12.17 fi Molecular basis of cell cycle regulation ๏ Oscillating protein system ‣ Cyclin-dependent kinases (CDK) Example: MPF Put phosphate groups on other proteins to activate/inhibit them Signals to downstream proteins carrying out cell cycle ‣ Cyclins Regulatory proteins Expressed then degraded Campbell g 12.16 fi Molecular basis of cell cycle regulation ๏ Oscillating protein system ‣ Cyclin-dependent kinases (CDK) ‣ Cyclins ๏ Cyclin = decision molecule ‣ Cyclins activate CdKs Binds to CdK to switch it ON Different CdK and cyclin pairs for each checkpoint ‣ Produced in response to signals inside and outside cell ‣ Degraded after use = timer Campbell g 12.16 fi Cancer and cell cycle control Cancer is a loss of cell cycle control ๏ Cancer ‣ Uncontrolled cell growth and division ‣ Cancer cells ignore checkpoints ๏ Normal cells sense their neighbourhood ‣ Anchorage and density dependence ‣ Block checkpoint to stop growing and dividing Campbell g 12.19 fi Cancer cells become transformed ๏ Cancer ‣ Uncontrolled cell growth and division ๏ Normal cells sense their neighbourhood ๏ Transformation ‣ Mutations leading to loss of cell cycle control ‣ Highly complex effects ‣ Cells keep on attempting to grow and divide Campbell g 12.19 fi Summary of lecture ๏ Cell division ‣ Genetically identical daughter cells ‣ Mitosis separates replicated sister chromatids ๏ Cell cycle ‣ 4 phases: G1, S, G2, M ‣ Interphase and mitosis ๏ Mitosis ๏ Cell cycle control ‣ Molecular mechanism ‣ Loss of regulation can lead to cancer Learning outcomes for lecture ๏ On successful completion of this lecture, you will be able to: ‣ Explain the cell cycle as a loop of phases ‣ Illustrate the stages in mitosis using diagrams ‣ Contrast mitosis with prokaryotic binary ssion ‣ Describe the molecular mechanism of checkpoints underlying control of the cell cycle ‣ Explain how cancer involves a loss of cell cycle control fi