DNA and Epigenetics
Describe the inheritance of mitochondrial DNA
Differentiate between active and passive membrane transport
Differentiate between the following forms of signaling: Paracrine, Autocrine, Synaptic, Endocrine.
Compare and contrast euchromatin and heterochromatin
Which of the following is NOT a key function of p53?
Glucose metabolism
What are the two most common forms of DNA variation in the human genome?
What are the 3 major classes of cytoskeletal proteins?
Actin microfilaments
5-9nm; Control cell shape and movement
Intermediate filaments
10nm; Provide tensile strength
Microtubules
25nm; Various functions including as mooring lines for transport, chromatid segregation during mitosis; flagella function
What are the different types of signals that cells respond to? Provide at least 3.
- Danger (cell damage, pathogens)
- Cell-cell communication (i.e. through gap junctions)
- Cell-ECM contacts (i.e. through integrins)
- Secreted molecules (growth factors, cytokines, hormones, etc…)
Name the phases of the cell cycle and broadly what occurs in each.
What is the Warburg effect?
- Propensity for tumor cells to undergo aerobic glycolysis rather than aerobic phosphorylation, even when adequate oxygen is present
- Less energy-rich process, but results in the generation of key building blocks for new cells
List 2 epigenetic modifications that do NOT involve histones
What are the 3 basic types of cell-cell junctions?
1. Occluding/Tight junctions
Form impermeable para-cellular barrier
2. Anchoring/Adherens Junctions
Mechanical link between adjacent cells and their cytoskeletons
3. Communicating/Gap junctions
Permit the diffusion of chemical or electrical signals between cells.
What are the two major forms of extracellular matrix?
1. Interstitial matrix
- Semi-fluid scaffold for tissue to grow upon
- Provides some cushioning for contractile structures (i.e. bowel, bladder, surrounding vessels)
2. Basement membrane
- Highly organized ECM around epithelial and endothelial elements
- Largely composed of type IV collagen and laminin
What is the definition of a stem cell? What are the major types?
Cells that can self-renew and become differentiated
Compare and contrast the site of origin for excreted/membrane proteins, cytoplasmic proteins and steroid hormones.
List 3 ways that histones may be modified through epigenetic means.
Compare and contrast the function of lysosomes, proteosomes and peroxisomes
1. Lysosomes
- Play a role in digesting engulfed macromolecules or microorganisms
2. Proteosomes
- Digest cytosolic proteins; particularly those which have been ubiquitinated.
3. Peroxisomes
- Responsible for digestion of long-chained fatty acids
Outline the 2 major pathways for endocytosis
1. Caveolae-mediated
- Non-coated plasma membrane invaginations (“Little caves”)
2. Receptor-mediated
- Specialized areas of plasma membrane (Clathrin-coated pits)
- Macromolecule binding leads to conformational change and introduction of Clathrin-coated vesicles.
What are the two types of cell division through which stem cells renew their populations?
1. Asymmetric division
- One daughter cell undergoes differentiation, while the other self-renews without differentiation
2. Symmetric division
- Both daughter cells divide without differentiating
Why do patients with scurvy bleed from old scars and heal poorly?
1. Collagen is key to maintaining the structural integrity of connective tissue
2. Fibrillar collagens cross-link via covalent bonds formed via lysine hydroxylation.
3. Lysyl hydroxylase, which catalyses this process, is dependent on Vitamin C
4. Therefore, VitC defiency à No hydroxylation à No covalent bonds à No tensile strength in tissues à Bleeding and poor wound healing
5. The same concept applies to Osteogenesis imperfecta and forms of Ehlers-Danlos Syndrome
What are the 5 main classes of functional noncoding genetic elements?
What are the three main families of ECM proteins?
1. Fibrous structural proteins
- I.e. collagens and elastin
- Provide tensile strength
2. Water hydrated gels
- Proteoglycans and hyaluronic acids
- Provide compression resistance and lubrication
3. Adhesive glycoproteins
- i.e. fibronectin
- Allow for cohesion between ECM elements and cells
Differentiate the roles of VEGF-A, VEGF-B, VEGF-C and VEGF-D
1. VEGF-A:
- The main one (classically referred to simply as VEGF)
- Involved in angiogenesis following injury and in tumors
2. VEGF-B:
- Involved in embryonic vascular development (alongside placental Growth Factor (PlGF))
3. VEGF-C and VEGF-D:
- Involved in angiogenesis and lymphatic development (lymphangiogenesis)
List 5 growth factors involved in tissue repair
1. Epidermal Growth Factor (EGF)
2. Transforming Growth Factor (TGF)
3. Hepatocyte Growth Factor
4. Vascular Endothelial Growth Factor
5. Platelet Derived Growth Factor (PDGF)
6. Fibroblast Growth Factor (FGF)
7. Transforming Growth Factor Beta (TGF-B)
8. Keratinocyte Growth Factor (KGF)
Broadly, define TGF-B and outline its main functions
Transforming Growth Factor Beta