Overview

Question 1

ENCODE (Ency­clopedia of DNA Elements) project

Answer 1

A 2007 initiative to identify all regions of a genome that could be ascribed some function

Question 2

How much of the genome is devoted to regulating gene expression or has some functional activity - related to gene expression?

Answer 2

About 80%

Question 3

Noncoding regulatory RNAs

Answer 3

Approximately 60% of the genome; RNAs that are never translated into protein, but which nevertheless can regulate gene expression through a variety of mechanisms. The two best-studied varieties are micro-RNAs and long noncoding RNAs

Question 4

P arm of a chromatid

Answer 4

The short arm

Question 5

Q arm of a chromatid

Answer 5

The long arm

Question 6

Enhancers

Answer 6

regulatory elements that can modulate gene expression over distances of 100 kB or more by looping back onto promoters and recruiting additional factors that are needed to drive the expression of pre-mRNA species

Question 7

The _____ sequences are subsequently spliced out of the pre-mRNA to produce the definitive message that is translated into protein

Answer 7

intronic

Question 8

The most common forms of DNA variation in the human genome

Answer 8

single-nucleotide polymorphisms (SNPs) and copy number variations (CNVs)

Question 9

Biallelic

Answer 9

only two choices exist at a given site within the population, such as A or T; common in SNPs

Question 10

linkage disequilibrium

Answer 10

where a genetic element is a useful marker of disease, because it is located in close proximity with a genetic element that causes disease

Question 11

CNVs

Answer 11

genetic variation consisting of different numbers of large contiguous stretches of DNA from 1000 base pairs to millions of base pairs

Question 12

What percentage of CNVs underlie gene-coding sequences?

Answer 12

Approximately 50%

Question 13

Nucleosomes

Answer 13

DNA segments 147 base pairs long that are wrapped around a central core structure of highly conserved low molecular weight proteins called histones

Question 14

heterochromatin

Answer 14

cytochemically dense and transcriptionally inactive

Question 15

euchromatin

Answer 15

cytochemically dispersed and transcriptionally active euchromatin

Question 16

Chromatin writing complexes

Answer 16

carry out more than 70 different histone modifications generically denoted as marks . Such covalent alterations include methylation, acetylation, or phosphorylation of specific amino acid residues on the histones.

Question 17

Chromatin remodeling complexes

Answer 17

can reposition nucleosomes on DNA, exposing (or obscuring) gene regulatory elements such as promoters

Question 18

Histone acetylation

Answer 18

Lysine residues are acetylated by histone acetyl transferases (HAT), whose modifications tend to open up the chromatin and increase tran­scription

Question 19

Histone methylation

Answer 19

Both arginines and lysines may be methylated; variable effect on whether this enables or represses gene transcription

Question 20

Histone H1

Answer 20

sits on the 20-80 nucleotide linker DNA between nucleosomes and helps stabilizes the overall chromatin architecture

Question 21

How long are long non-coding RNAs?

Answer 21

> 200 nucleotides in length.

Question 22

miRNAs

Answer 22

function primarily to modulate the translation of target mRNAs into their corresponding proteins. Posttranscriptional silencing of gene expression by miRNA is a fundamental and well-conserved mechanism of gene regulation present in all eukaryotes (plants and animals) .

Question 23

DICER

Answer 23

successive processing of pre-miRNAs by this enzyme generates mature single-stranded miRNAs of 21 to 30 nucleotides that are associated with a multiprotein aggregate called RNA-induced silencing complex (RISC)

Question 24

RISC MOA

Answer 24

Base pairing between the miRNA strand and its target mRNA directs the RISC to either induce mRNA cleavage or repress its translation.

Question 25

Perfect match between RISC-bound mRNA and miRNA induces

Answer 25

Cleavage

Question 26

An imperfect match between RISC-bound mRNA and miRNA induces

Answer 26

Repression of translation

Question 27

Small interfering RNAs (siRNAs)

Answer 27

Synthetic complexes that can bind with RISC for study purposes; under investigation for possible therapeutic use

Question 28

XIST

Answer 28

lncRNA transcribed from the X chromosome that plays an essential role in physiologic X chromosome inactivation

Question 29

Functions of lncRNAs

Answer 29

facilitate TF binding (gene activation) pre-emptively bind TF binding (prevent gene activation) May direct acetylases or methylases May act as scaffolding ot stabilize multi-subunit complexes

Question 30

New proteins destined for the plasma membrane or points beyond are synthesized in the ___ and physically assembled in the ___

Answer 30

RER; Golgi apparatus

Question 31

proteins intended for the cytosol are synthesized where?

Answer 31

On free ribosomes

Question 32

SER

Answer 32

Abundant in gonads and liver; steroid hormone and lipoprotein synthesis, as well as for the modification of hydrophobic compounds (for example, drugs) into water-soluble molecules for export

Question 33

3 sites of catabolism within the cell

Answer 33

Lysosomes Proteasomes Peroxisomes

Question 34

intracellular organelles that contain degradative enzymes that permit the digestion of a wide-range of macromolecules, including proteins, polysaccharides, lipids, and nucleic acids

Answer 34

Lysosomes

Question 35

a specialized type of “grinder” that selectively chews up denatured proteins, releasing peptides. In some cases the peptides so generated can be presented in the context of class I major histocompatibility molecules

Answer 35

Proteasomes

Question 36

play a specialized role in the breakdown of fatty acids, generating hydrogen peroxide in this process.

Answer 36

Peroxisomes

Question 37

shuttle internalized material to the appropriate intracellular sites or direct newly synthesized materials to the cell surface or targeted organelle

Answer 37

Endosomal vesicles

Question 38

Power cell via oxidative phosphorylation, production of ATP Site of heme synthesis Can initate and regulate apoptosis

Answer 38

Mitochondria

Question 39

Phosphatidylinositol

Answer 39

on the inner membrane leaflet can be phosphorylated, serving as an electrostatic scaffold for intracellular proteins; alternatively, polyphosphoinositides can be hydrolyzed by phospholipase C to generate intracellular second signals like diacylglycerol and inositol trisphosphate.

Question 40

is normally restricted to the inner face where it confers a negative charge involved in electrostatic protein interactions; however, when it flips to the extracellular face, which happens in cells undergoing apoptosis (programmed cell death), it becomes an “eat me” signal for phagocytes. In the special case of platelets, it serves as a cofactor in the clotting of blood.

Answer 40

Phosphatidylserine

Question 41

important in cell-cell and cell-matrix interactions, including inflammatory cell recruitment and sperm-egg interactions.

Answer 41

Gycolipids

Question 42

phosphatidylcholine and sphingomyelin are overrepresented in the ____ leaflet, and phosphatidylserine (negative charge) and phosphatidylethanolamine are predominantly found on the ____ leaflet

Answer 42

outer; inner

Question 43

have one or more relatively hydrophobic α-helical segments that traverse the lipid bilayer. Integral membrane proteins typically contain positively charged amino­acids in their cytoplasmic domains, which anchor the proteins to the negatively charged head groups of membrane phospholipids.

Answer 43

Integral or transmembrane proteins

Question 44

Insertion into the membrane may occur through ______ anchors on the extracellular face of the membrane.

Answer 44

glycosylphosphatidylinositol (GPI)

Question 45

Glycocalyx

Answer 45

The extracellular face of the plasma membrane that is diffusely studded with carbohydrates, not only as complex oligosaccharides on glycoproteins and glycolipids, but also as polysaccharide chains attached to integral membrane proteoglycans.

Question 46

Lipid bilayers are impermeable to

Answer 46

passage of polar molecules of greater than 75 daltons in mass, even those that are only slightly larger, such as glucose. Lipid bilayers are also impermeant to ions, no matter how small, due to their charge and high degree of hydration

Question 47

channel proteins and carrier proteins may be used for transport of

Answer 47

low molecular weight species (ions and small molecules up to approximately 1000 daltons)

Question 48

___ are used when concentration gradients can drive the solute movement. ____ are required when solute is moved against a concentration gradient.

Answer 48

Channels; carriers

Question 49

endocytose extracellular fluid, membrane proteins, and some receptor bound molecules (e.g., folate) in a process driven by caveolin proteins concentrated within lipid rafts ( potocytosis

Answer 49

Cavelolae

Question 50

Phagocytosis

Answer 50

non-clathrin-mediated membrane invagination of large particles—typically by specialized phagocytes (e.g., macrophages or neutrophils).

Question 51

Pinocytosis of extracellular fluid and most surface receptor-ligand pairs involves ____ . After internalization, the _____ dissociates and can be re-used, while the resulting vesicle progressively matures and acidifies.

Answer 51

clathrin-coated pits and vesicles; clathrin

Question 52

Transcytosis

Answer 52

transcellular endocytotic transport of solute and/or bound ligand from one face of a cell to another

Question 53

the process by which membrane-bound vesicles fuse with the plasma membrane and discharge their contents to the extracellular space

Answer 53

Exocytosis

Question 54

pumps polar compounds (e.g., chemotherapeutic drugs) out of cells and may render cancer cells resistant to treatment

Answer 54

MDR; a transporter ATPase

Question 55

How does hydropic degeneration occur?

Answer 55

Since the cytosol is rich in charged metabolites and protein species that attract a large number of counterions that tend to increase the intracellular osmolarity, cells need to constantly pump out small inorganic ions (e.g., Na + and Cl −), typically through the activity of the membrane sodium-potassium ATPase, lest they become overhydrated. Loss of the ability to generate energy (e.g., in a cell injured by toxins or ischemia) therefore results in osmotic swelling and eventual rupture of cells.

Question 56

noncoated plasma membrane invaginations associated with GPI-linked molecules, cyclic adenosine monophosphate (cAMP) binding proteins, SRC-family kinases, and the folate receptor

Answer 56

Caveolae

Question 57

Internalization of caveolae with any bound molecules and associated extracellular fluid

Answer 57

Potocytosis or "cellular sipping"

Question 58

a fluid-phase process during which the plasma membrane invaginates and is pinched off to form a cytoplasmic vesicle

Answer 58

Pinocytosis

Question 59

rapidly invaginates and pinches off to form a clathrin-coated vesicle ; trapped within the vesicle is a gulp of the extracellular milieu and in some cases receptor bound macromolecules

Answer 59

Clathrin-coated pit

Question 60

Macromolecules that enter the cell via receptor-mediated endocytosis

Answer 60

LDL and transferrin to release cholesterol and iron. A defect in transport of LDL is responsible for familial hypercholesterolemia.

Question 61

Nuclear lamins

Answer 61

important not only for maintaining nuclear morphology but also for regulating normal nuclear transcription

Question 62

Diseases caused by mutations in lamins

Answer 62

certain froms of muscular dys­trophy to progeria, a disease of premature aging

Question 63

anterograde (− to +) transport proteins that use ATP to move vesicles, organelles, or other molecules around cells along microtubules

Answer 63

kinesins

Question 64

retrograde (− to +) transport proteins that use ATP to move vesicles, organelles, or other molecules around cells along microtubules

Answer 64

dyneins

Question 65

mechanically attach cells—and their intracellular cytoskeletons—to other cells or to the extracellular matrix (ECM).

Answer 65

Anchoring junctions (desmosomes)

Question 66

Mechanical adhesion focus between two cells

Answer 66

spot desmosome or macula adherens

Question 67

Mechanical attachment point for the cell to the ECM

Answer 67

hemidesmosome

Question 68

Broad bands of mechanical attachment points in between cells

Answer 68

belt desmosomes

Question 69

E-cadherins

Answer 69

Transmembrane adhesion molecules in belt desomsomes

Question 70

Transmembrane adhesion molecules in spot desomsomes

Answer 70

desmogleins and desmocollins

Question 71

large (>100 proteins) macromolecular complexes that can be localized at hemidesmosomes, and include proteins that can generate intracellular signals when cells are subjected to increased shear stress, such as endothelium in the bloodstream, or cardiac myocytes in a failing heart.

Answer 71

Focal adhesion complexes

Question 72

mediate the passage of chemical or electrical signals from one cell to another

Answer 72

communicating/gap junctions

Question 73

reactive SER hyperplasia

Answer 73

can be caused by repeated exposure to compounds that are metabolized by the SER (e.g., phenobarbital catabolism by the cytochrome P-450 system)

Question 74

What is the sarcoplasmic reticulum?

Answer 74

Specialized SER - responsible for the cyclical release and sequestration of calcium ions that regulates muscle contraction and relaxation, respectively

Question 75

Responsible for sequestering intracellular calcium in the cell

Answer 75

SER

Question 76

Lysosomal enzymes are initially synthesized in the ER lumen and then tagged with a _____ residue within the Golgi apparatus

Answer 76

mannose-6-phosphate (M6P)

Question 77

In this process.... Through poorly understood mechanisms, obsolete organelles are corralled by a double membrane derived from the endo­plasmic reticulum; the membrane progressively expands to encircle a collection of structures and forms an autophagosome which then fuses with lysosomes and the contents are catabolized.

Answer 77

Autophagy

Question 78

How are sensecent organelles or denatured proteins targeted for autophagy?

Answer 78

LC3 proteins (microtubule-associated protein 1A/1B-light chain 3).

Question 79

What does the inner membrane of the mitochondrion contain?

Answer 79

enzymes of the respiratory chain folded into cristae

Question 80

What happens in the intermembrane space of the mitochondrion?

Answer 80

site of ATP synthesis

Question 81

studded with porin proteins that form aqueous channels permeable to small (

Answer 81

Outer mitochondrial membrane

Question 82

How are mitochondria stimulated to trigger necrosis of the cell?

Answer 82

External cellular injury (toxin, ischemia, trau­ma) can damage mitochondria, inducing the formation of mitochondrial permeability transition pores in the outer membrane. These channels allow the dissipation of the proton potential so that mitochondrial ATP generation fails and the cell dies.

Question 83

transcription factors that are activated by lipid-soluble ligands that can easily cross the plasma membrane

Answer 83

Intracellular receptors

Question 84

Examples of receptor tyrosine kinases (RTKs)

Answer 84

receptors for insulin, epidermal growth factor, and platelet derived growth factor

Question 85

Review - Wnt, Frizzled, Dissheveled

Answer 85

Nor­mally, β-catenin is constantly targeted for ubiquitin-directed proteasome degradation. However, Wnt binding to Frizzled (and other co-receptors) recruits yet another intracellular protein ( Disheveled ) that leads to disruption of the degradation-targeting complex. The stabilized pool of β-catenin molecules then translocates to the nucleus, where β-catenin forms a transcriptional complex

Question 86

produced by macrophages and a variety of epithelial cells, and are mitogenic for hepatocytes, fibroblasts, and a host of epithelial cells.

Answer 86

EGF and TGF-a

Question 87

produced by fibroblasts and most mesenchymal cells, has mitogenic effects on hepatocytes and most epithelial cells, including biliary, pulmonary, renal, mammary,and epidermal. Also acts as a morphogen in embryonic development (i.e., it influences the pattern of tissue differentiation), promotes cell migration (hence its designation as scatter factor ), and enhances hepatocyte survival.

Answer 87

HGF

Question 88

receptor for HGF, it has intrinsic tyrosine kinase activity and is frequently overexpressed or mutated in tumors, particularly renal and thyroid papillary carcinomas.

Answer 88

MET

Question 89

produced by platelets, activated macrophages, endothelium, smooth muscle cells, and a variety of tumors. Receptors have intrinsic tyrosine kinase activity; induces fibroblast, endothelial, and smooth muscle cell proliferation and matrix synthesis, and is chemotactic for these cells (and inflammatory cells), thus promoting recruitment of the cells into areas of inflammation and tissue injury.

Answer 89

PDGF

Question 90

induces angiogenesis by promoting endothelial cell migration, proliferation (capillary sprouting), and formation of the vascular lumen; also induce vascular dilation and increased vascu­lar permeability

Answer 90

VEGF

Question 91

VEGF inducers

Answer 91

Primarily HIF-1, but also TGF-a and PDGF

Question 92

disorder of inappropriate angiogenesis and vascular permeability that causes adult-onset blindness; treated with anti-VEGF Ab

Answer 92

Age-related macular degeneration

Question 93

produced by platelets, endothelium, and mononuclear inflammatory cells; is secreted as a precursor that requires proteolysis to yield the bio­logically active protein. Pleiotropic, but drives scar formation, and applies brakes on the inflammation that accompanies wound healing

Answer 93

TGF-β

Question 94

produced by mesenchymal cells (like fibroblasts); present in the spaces between cells in connective tissue, and between parenchymal epithelium and the underlying supportive vascular and smooth muscle structures

Answer 94

Interstitial matrix

Question 95

Major constituents of basement membrane

Answer 95

amorphous nonfibrillar type IV collagen and laminin

Question 96

On this protein, highly negatively charged sulfated sugars on the “bristles” recruit sodium and water to generate a viscous, but compressible matrix

Answer 96

Proteoglycans