UNIT II: Patterns of Inheritance (Mendelian genetics; also cell division and cell cycle)1. Describe a duplicated (or “replicated”) chromosome.Replicated eukaryotic chromosome: 2 sister chromatids joined at a centromere, by cohesion proteins 2. To what does the cell cycle refer and what “events” (stages, steps, etc.) are involved?The Cell Cycle: is the life of a cell, it has two components: cell growth & cell division; it isalso a continuous process. 1. Interphase 3 stages: G1, S, G2G1: Cell is growing, metabolizing (i.e., genes are being regulated)S: DNA synthesis (chromosomes replicate)G2: After DNA replicates, cell must synthesize proteins & structures to prepare for cell division. (e.g. centrosome replicates)- This is a “microtubule organizing center”- Each centrosome consists of a pair of cylindrical centrioles: - These synthesize microtubules needed for spindle formation- Centrioles are absent in plant cells2. M or Mitotic phase: 2 parts = mitosis & cytokinesis- In “M”, the nucleus & cytoplasm divide by mitosis & cytokinesis into 2 daughter cells (each with the original # of chromosomes)3. Why do cells/organisms need to regulate or control the cell cycle?The cell cycle must be regulated so a cell knows when to divide to make new cells (for example, for growth or repair), or when not to divide (when it remains in G0 and simply serve its function depending on the type of cell). Normal cells must also respond to signals that cause them to exhibit anchorage dependence (so a cell stops dividing once it loses contact with it’s usual substrate) and to exhibit density-dependent inhibition (so a cell stops dividing once cell density reaches some maximum).The cell cycle must also be regulated so that a cell doesn’t replicate damaged DNA. For example, the changing concentration of a particular cyclin allows it to interact with an ever-present particular CDK, forming the MPF signal required to move a cell through the G2 checkpoint. Another example when PDGF serves as an external growth-factor signal stimulating a cell to divide. Another example is when the P53 tumor-suppressing gene is activated when DNA is damaged, and passage into the “S” stage is restricted until DNA is repaired (if possible).4. How do cells/organisms regulate or control the cell cycle? Explain the role of checkpoints. Explain the chemical control system that gets cells through the G2 checkpoint.There are molecular signals in the cytoplasm that regulate the cell cycle. The cell cycle is regulate at various checkpoints: G1, G2, and M checkpoints - Whether cell cycle stops or proceeds through a checkpoint depends on what chemical signals are present. 1. G1 restriction checkpoint: cell cycle pauses (i.e., cell “hangs out” just doingits job in G0) if directed to do so by signals; or other signals can direct the cell to pass the checkpoint. And enter “S”, or even undergo apoptosis.2. G2 checkpoint: if preparations for cell division are “ok”, then signals molecules direct the cell to enter the “M” (mitotic) phase. Cell cycle is controlled by regulatory proteins that act as signal molecules. - One particular signal needed to pass the G2 checkpoint is MPF. MPF: one particular cyclin/Cdk complex (cyclin + Cdk = MPF) needed to get thru G2 checkpoint. - Cyclins: proteins the fluctuate in concentration throughout the cell cycle- Cdks: various cyclin-dependent-kinases; they bind to and activate cyclins to get though a checkpoint. - Cdk proteins are always present - Kinases: proteins in signaling transduction that phosphorylate & activate other proteinsExample: passage through the G2 checkpoint. - Synthesis of G2 cyclin fluctuates cyclically through the cell cycle- When the amount of the G2 cyclin gets high, it binds to & is activated by a specific Cdk & forms a Maturation-Promoting Factor (MPF) signal to proceed through the G2 checkpoint. - Once past the checkpoint, the cyclin part of MPF is degraded but the Cdk partbecomes available again and initiates mitosis. Passage through the cell cycle involves two intertwined mechanism:1. The repeated internal synthesis and degradation of various cyclin “clock” molecules. 2. Uses feedback from other internal signals (i.e. hormones) & external signals (i.e. growth factors) that adjust the activity of cyclins as needed. - i.e. other signals can regulate the internal cyclin “clock”Example: human fibroblast cell growth & division- Fibroblast cells (connective-tissue) secrete an extracellular matrix (e.g. collagen)- An external growth factor signal called PDGF (platelet-derived growth factor) stimulates fibroblast cell division (mitosis)- If no PDGF, cells remain at G0 (don’t divide)- If PDGF is present, it signals cells to proceed through G1 checkpoint & enter “S” (to divide). - e.g., a growth-factor signal that initiates a signal transduction pathway that activates a transcription factor to express a gene. 5. What is the general purpose of mitotic cell division? Describe the step-wise process of mitotic cell division. Compare the number of chromosomes before the start of mitosis, at each step, and at the end.Mitosis: division of the nucleus that preserves the parental chromosome # in both daughter cells1. Prophase- Centrosomes move to opposite poles- Spindle microtubules start to lengthen - Nuclear membrane starts to dissolve- Nucleolus disintegrates- “Diffuse” DNA that already replicated during “S” begins to “condense” into distinct chromosomes- A replicated chromosome = 2 sister chromatids joined at a centromere (joinedby cohesion proteins)2. Pro-metaphase- Nuclear membrane is gone - Chromosomes are clearly distinct- A kinetochore appears at each centromere- Spindle apparatus is now complete:- Non-kinetochore polar microtubules (pole to pole)- Kinetochore microtubules (pole to kinetochore)- Aster microtubules (from centrosome to cell edge)3. Metaphase- Spindle microtubules move chromosomes - Chromosomes line up SINGLE FILE at the midline, or cell equator “metaphase plate”4. Anaphase- Centromere splits- Spindle microtubules pull apart sister chromatids toward opposite poles- Tubulin subunits of a microtubule breakdown- Each separated chromatid is now called a distinct chromosome5. Telophase- Spindle disassembles- Nuclear membrane reforms- Nucleolus reappears - Mitosis, or nuclear division, is now completeCytokinesis- Cell membrane pinches in (invaginates) at cleavage furor- Cytoplasmic division is now
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