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1 Mutations Chapter 5 Cellular Functions Lecture 3: and Cell Division Most DNA mutations alter the protein product May Make it function better (rarely) Change its function Reduce its function Make it non-functional Example: Cancer Mutations Mutations in proteins that regulate cell growth and division Unregulated cell growth To understand cancer, we need to understand normal cell life cycle Begins and ends with division events = process of division for most cells Interphase = time between division events Growth allows a single fertilized egg to become a relatively large multicellular organism Adults have more cells than babies! Replacement cells, like those of the skin, wear out at a predictable pace Small intestine 1

2 Reproduction most multicellular organisms produce egg and sperm cells that permit them to produce offspring Meiosis more on that later! Repair accidents happen! Interphase is the phase between cell divisions Cell spends most of its time here Cell performs its functions here Transcription (chromatin unwound) Translation Interphase Interphase has 3 stages as the cell prepares for division G 1 phase 8-12 hours (or longer) Growth 1 or Gap 1 Phase Cell manufactures cytoskeletal elements and organelles for 2 cells Mitochondria divide Exiting the cell cycle G 0 Phase After G1, some cells enter a quiescent state Some re-emerge emerge after a time Some remain quiescent for the life of the organism (muscle cells, neurons) Interphase has 3 stages as the cell prepares for division S phase 6-8 hours Interphase Synthesis phase Chromosomes are duplicated 2

3 Interphase Interphase has 3 stages as the cell prepares for division G 2 phase 2-5 hours Growth 2 phase Period of rapid cell growth and last-minute protein synthesis Cell is preparing to divide Some cells skip this stage Frog embryos, cancer M Phase Interphase ends when cells begin M phase and cytokinesis Duplication and division of nucleus and the entire cell Has its own steps (which we will cover in a minute) Checkpoints Exist to make sure a cell is healthy, normal Don t want to duplicate mutated DNA! Three major checkpoints G 1 /S check for sufficient growth, damaged DNA, sufficient preparations G 2 /M check for DNA damage in duplicated chromosomes, is everything ready? M check for proper spindle formation just before cell divides Checkpoints Cyclin and cyclin-dependent kinase Proteins involved in cell cycle regulation Depends on tumor suppressor called p53 Normal cell: p53 and Cancer DNA p53 Cell cycle Repair Damaged Produced Arrest Cancer cell: DNA No p53 Uncontrolled Damaged Produced Cell growth 3

4 p53 is frequently mutated in cancer Cancer can occur in any tissue Most common (National Cancer Institute) 1. Prostate 2. Breast 3. Lung 4. Colorectal p53 and Cancer Cancer treatments target rapidly dividing cells Problem: some normal cells divide rapidly Small intestine Cells for hair growth Bone marrow Leads to common side effects of cancer treatments Weight loss Hair loss Anemia Cancer Primary type of cell division Used by somatic cells Produces two genetically identical daughter cells Replication must occur prior to mitosis Helicase unwinds DNA strands Strands separate at replication fork Each strand used as a template DNA polymerase makes missing strands Two DNA strands are in opposite orientations Antiparallel Problem: DNA polymerase can only add nucleotides in one direction (5 to 3 ) Leading strand synthesized continuously Lagging strand synthesized in short pieces that are joined together 4

5 Newly synthesized DNA molecules are called chromatids Two identical molecules are called sister chromatids Chromosomes Sister chromatids become attached to each other at the centromere Condense to become chromosomes Chromosomes Chromosomes are large enough to be seen by light microscope Chromosomes are only present when a cell is preparing to divide Takes place in several stages Do not memorize for this class, but someone will want you to eventually (PMAT) In here: know the process of mitosis and what steps must happen, without memorizing phase names Prophase Centrioles move to opposite poles Nuclear membrane breaks down Metaphase Duplicated chromosomes line up at metaphase plate Microtubles attach to cenromeres at mitotic spindle Additional checkpoint here 5

6 Anaphase Centromeres split Half of chromosomes move toward each pole Cell membrane begins to pinch at center Telophase Cell membrane constricts at center Nuclear membranes re-form around chromosomes Cytokinesis completed Two daughter cells with identical DNA Far more important than knowing the names for each phase of mitosis is understanding what happens to the DNA Phase of the Human Cell Chromosome Number Significant Event(s) G1 (and G0) 46 Duplicate organelles S 92 DNA replication 92 Sister chromosomes separate Cytokinesis 46 Daughter cells produced M phase 6

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