The Cell As A Unit Of Health And Disease Flashcards
What are the five major classes of functional non-protein-coding sequences in the human genome?
- Promoter and enhancer regions
- Binding sites for factors that organise and maintain higher order chromatin structures
- Noncoding regulatory RNAs
- Mobile genetic elements
- Special structural regions of DNA, e.g. telomeres and centromeres
Describe the two most common forms of DNA variation in the human genome
-Single nucleotide polymorphisms (SNPs) - almost always bialleic, randomly spread across genome, most have only weak effect, if any, on disease susceptibility, can be used as markers if co-inherited.
-Copy number variations (CNVs) - different numbers of large contiguous stretches of DNA 1000 to millions of BPs, can be bialleic, have multiple variants, be duplicated or deleted, about 50% involve gene-coding sequences.
Name the substance acted on and the resulting effect of the following marking processes:
1. Histone methylation
2. Histone acetylation
3. Histone phosphorylation
4. DNA methylation
- Lysines and arginines. Transcriptional activation or repression
- Lysine residues. Generally increases transcription via opening chromatin
- Serine residues. Open DNA for transcription or condense DNA making it inactive
- DNA. High levels typically result in transcriptional silencing
Micro-RNA are 22 nucleotides on average in length. How do they cause post-transcriptional silencing of gene-expression?
By associating with RNA-induced silencing complexes and then base paring with the target mRNA which directs the RISC to either induce mRNA cleavage or repress its translation.
Name four ways long non-coding RNA (>200 nucleotides in length) can modulate gene expression
- Gene activation
- Gene suppression
- Promote chromatin modification
- Assembly of protein complexes
What is XIST?
A long non-coding RNA transcribed from the X chromosome that binds to chromatin and restricts RNA polymerase from accessing coding genes within that region. Has an essential role in physiologic X chromosome inactivation in females.
What discovery has made high-fidelity genome editing a possibility?
CRISPR (clustered regularly interspaced short palindromic repeats) and CRISPR- associated genes (Cas) from prokaryotes.
Introduction of guide RNA and the Cas enzyme can induce double stranded DNA cleavages at specific sites. These can repair randomly or with introduced new genetic material
Name the face of the plasma membrane the following phospholipids tend to reside:
-Phosphatidylchlorine
-Phosphatidylinositol
-Phosphatidylethanolamine
-Phosphatidylserine
-Sphingomyelin (not a phospholipid)
Mostly outer - Phosphatidylchlorine, Sphingomyelin
Mostly inner - Phosphatidylethanolamine, Phosphatidylserine
Both faces - Phosphatidylinositol
Which phospholipid becomes a potent “eat me” signal during programmed cell death if flipped to the extra cellular leaflet of the plasma membrane.
Phosphatidylserine
What are the main constituents of “lipid rafts”?
Glycosphingolipids and cholesterol
What are the four main mechanisms by which proteins associate with the lipid bilayer?
- As integral or transmembrane proteins by having one or more relatively hydrophobic a-helical segments.
- Through post-translational addition of prenyl groups or fatty acids that insert into the cytosolic side of the plasma membrane.
- Anchoring by glycosylphosphatidylinositol (GPI) tails on the extra cellular face.
- Non-covalent association with transmembrane proteins
What are the criteria for molecules to be able to passively diffuse through the plasma membrane (at any rate)?
Small non-polar, hydrophobic, or polar and < 75Da in size
Which class of cytoskeletal proteins can be helpful in assigning a cell of origin for poorly differentiated tumours?
Intermediate filaments (they have characteristic tissue-specific patterns of expression)
Briefly summarise the function of tight junctions
Seal adjacent epithelial cells together to create a continuous barrier that restricts the paracellular movement of ions and other molecules. It also represents the boundary that separates apical and basolateral membrane domains and helps to maintain cellular polarity.
What are two shared features of adherens junctions and desmosomes?
- anchoring junctions
- formed by homotypic extracellular interactions between transmembrane glycoproteins called cadherins, on adjacent cells.
What can explain the discohesive invasion pattern of some gastric cancers and lobular carcinomas of the breast?
Loss of the epithelial adherens junction protein E-cadherin.
(Adherens junctions are associated with intracellular actin microfilaments through which they can influence cell shape and motility)
Cadherins in desmosomes and integrins in hemidesmosomes are linked to intracellular intermediate filaments. What is one important function of this?
Allows extracellular forces to be mechanically communicated and dissipated over multiple cells.
What is the name of the protein complexes that can generate intracellular signals when cells are subjected to shear stress and where do they localise?
Focal adhesion complexes.
Localise at hemidesmosomes.
What does a gap junction consist of?
A dense planar array of 1.5 to 2nm pores (connexons) formed by a pair of hexamers of transmembrane connexin proteins.
What are the possible destinations of proteins and lipids synthesised in the endoplasmic reticulum?
-Transmembrane (plasma membrane or cellular organelle membranes inc the ER)
- Golgi body (ultimately for secretion)
