Cell Cycle - Introduction Key Concepts Cell division results in two identical cells During cell division the ability to organize DNA in time and space (location in the cell) is critical! The mitotic phase of the Cell Cycle alternates with a interphase Cell cycle is controlled by a molecular control system Key Questions that scientist want to understand:
Cell Cycle - Introduction Total genetic material is called the GENOME Prokaryotic Eukaryotic (human cells) Chromosomes 1 circular, + plasmids several linear DNA 4.6 million base pairs (BP) 3 Billion BP (human) Cell division time 20 minutes 24 hours Mechanism of division binary fission mitosis, cytokinesis Cell Division Duplicate of DNA with high fidelity Distribute DNA evenly to the 2 progeny (WITHOUT MISTAKES!!!) (Order of genes stays the same)
Cell Cycle - Introduction Somatic Cells all cells except for reproductive cells 200 Trillion cells in your body made by Mitosis and Cytokinesis! Reproductive cells (gametes) sperm and egg cells Meiosis variation of cell division that makes non-identical daughter cells Interesting facts 25,000,000 cells divide per minute in our bodies Every 8 seconds DNA suffers a break at least once! Some cells continuously divide (skin) Some cell types are quiescent, unless provoked (blood) Some cells never divide (muscle, neurons) Some cells are dead but still part of our body (hair, nails) Division leads to death, eventually! Control of cell division is control of cancer.
Stages of the Cell Cycle M G 1 G 2 S G 1 = Gap phase #1 : wait, grow S = synthesis of DNA G 2 = Gap phase #2 : checkpoints check to see if DNA is replicated fidelity Prepare cytoskelton for cytokinesis 5-6h 6h 12h M = Mitosis : divide the DNA and cytokinesis 30min.
Anatomy of a Eukaryotic Mitotic Chromosome DNA is bound by proteins: CHROMTIN Major type of protein is called HISTONES DNA is efficiently packed by wrapping around histones. In Mitosis : called SUPERCOILING
Anatomy of a Eukaryotic Mitotic Chromosome Chromatid = 1 Chromosome Telomeres Ends of DNA 0.5 µm Centromere where sister chromatids attach Sister chromatids (identical) Figure 12.4 Sister chromatids
Cell Cycle Dividing the DNA EVENLY between 2 cells 1. S-phase Duplicate DNA S 2. Attach to SPINDLE; microtubules hook on to centromere via KINETOCHORE (made of proteins) 3. Pull Chromatids apart (separate) using microtubule motors : Kinesins 4. Reform into 2 cells around DNA
Cell Cycle MITOSIS Interphase G1 : receive a signal to divide S : duplicate DNA G2: CENTRIOLES duplicated MITOSIS PROHASE PROMETAPHASE METAPHASE ANAPHSE DNA dondensed Centrioles seapated to opposite sides of nucleus Start spindle formation Nuclear enevelope fragments MTs can now bind at kinetochore centrioles are now at opposites sides Chromosomes lined up at middle of spindle called METAPHASE PLATE 2 sister chromatids are separated pulled apart to opposite spindle poles
Cell Cycle MITOSIS ANAPHSE TELOPHASE CYTOKINESIS 2 sister chromatids are separated pulled apart to opposite spindle poles chromatids well separated spindle pole disassembles nuclear envelope reforms around DNA Cleavage furrow forms - involves actin and myosin: contraction
Cell Cycle MITOSIS G 2 OF INTERPHASE PROPHASE PROMETAPHASE Centriole Duplicated Chromasomes (duplicated) Early mitotic spindle Centromere Fragments of nuclear envelope Kinetochore Figure 12.6 Nuclear envelope Plasma membrane Sister chromatids microtubule attaches to Kinetochore
Cell Cycle MITOSIS METAPHASE ANAPHASE TELOPHASE AND CYTOKINESIS Metaphase plate Cleavage furrow Nucleolus forming Figure 12.6 Spindle pole Daughter chromosomes Nuclear envelope reforming
Cell Cycle Checkpoints STOP and GO-ahead signals G1 checkpoint restriction point Wait for a growth factor signal? Sufficient energy? Sufficient space Internal timing of control system? After S-phase (replicated DNA) - G2 checkpoint Quality control: look for gaps in DNA i.e. is replication finished?????? Are microtubules, centrioles, cytoskeleton, and organelles ready???? M checkpoint Is DNA divided evenly?????
Cell Cycle Checkpoints STOP and GO-ahead signals G 1 checkpoint Control system S G 1 M G 2 M checkpoint Figure 12.14 G 2 checkpoint
Cell Cycle Checkpoints STOP and GO-ahead signals Most cells are actually waiting in G 0 until the right signal comes along Some cells stay in G 0 (e.g. neurons) G 0 G 1 checkpoint G 1 G 1 Figure 12.15
Cell Cycle Control System What controls the progression of the cell cycle? Molecular control System- that involves Checkpoints
Cell Cycle Evidence for a Control System Cells at different stages of cell cycle were fused together Experiment 1 Experiment 2 S G 1 M G 1 S S M M G1 cell initiated DNA replication S phase G1 cell initiated Mitosis without replicating its DNA
Kinase activity Cell Cycle the M-phase promoting Factor (MPF) - part of the control system M-phase promoting Factor (MPF) Cyclins allosteric regulators of CDKs Expressed cyclically Cyclin-dependent kinases (CDKs) kinase that is only active when bound to cyclin activator M G 1 S G 2 M G 1 S G 2 MPF activity M Cyclin Time
Cell Cycle and Cancer Cells that have lost there control over cell division! ~85% of cancer cells have a mutation in the DNA Lose a checkpoint control 15% - caused by virus: which induces S phase Benign tumor Cell still looks the same But has uncontrolled growth: Tumor Damages neighboring cells (tissues) Malignant tumor Cell becomes undifferentiated Uncontrolled growth Loses its attachment to neighbors Metastasis can spread thru the body Normal cell will stop dividing when they are crowded - Contact Inhibition! (Negative feedback mechanism)
More about Cell Cycle and Cancer Hallmarks of Cancer: 6 changes that happen to cancer cells Self-sufficiency in growth signals Cells produce their own growth signals Insensitivity to negative growth signals While normal cells respond to stop growth signals cancer cells do not Evasion of apoptosis (programmed cell death) Surrounding cells begin to die Acquisition of limitless proliferative capacity Uncontrolled cell growth Sustained Angiogenesis (blood supply) Cancer cells create their own blood supply by recruiting new blood vessels Tissue invasion and metastasis Move to other tissues and create new tumors
A TYPICAL FAMILY TREE OF INHERITED CANCER SYNDROME Individuals With Related Cancer
Inherited vs. Sporadic Cancer Inherited Cancer Syndrome: Sporadic Cancer: Germline mutation Somatic mutation Early onset Later in life More than one tumor Clonal tumor Rare One in four people
Accumulation of genetic alterations and the progression of Cancer