Chapter 1

Question 1

_______ are organized into P and Q arms where the ____ arms are shorter

_____ have lower GC content while ______ have more GC content and are where genes tend to localize.

Answer 1

Chromatids; P

Bands; interbands

Question 2

Differentiate heterochromatin vs euchromatin

Answer 2

Heterochromatin = densely packed, transcriptionally inactive

Euchromatin = dispersed, transcriptionally active

Question 3

Individual chromatin fibers are composed of a string of _______ — DNA wound around octameric _____ cores, connected via DNA linkers

Answer 3

Nucleosomes; histones

Question 4

Function of nucleosome

Answer 4

Nucleosomes form fundamental repeating units of chromatin, which is used to pack the genome into the nucleus while still ensuring appropriate access to it

Question 5

Promoters and enhancers provide binding sites for transcription factors. What is the difference between the 2?

Answer 5

Promoters = initiate gene transcription on same strand/upstream of their associated gene

Enhancers = modulate gene expression over distant sequences; recruit additional factors

Question 6

Mobile genetic elements called ______ serve to regulate genes and chromatin organization

Answer 6

Transposons

Question 7

2 most common variations in the human genome

Answer 7

SNPs = variants at single nucleotide positions; almost always biallelic; occur across genome within exons, introns, intergenic regions, coding regions; may or may not affect gene expression; serve as markers for disease

CNVs = different numbers of large contiguous stretches of DNA; may be biallelic or multiallelic; unknown effect on DNA susceptibility; likely account for much of phenotypic diversity in humans

Question 8

Epigenic factors associated with histone organization: Histone methylation

Answer 8

Occurs at Lys or Arg residues

May be associated with transcription activation or repression (but typically repression!)

Question 9

Epigenic factors associated with histone organization: histone acetylation

Answer 9

Occurs via HATs at Lys residues

Leads to increased transcription (reversed by HDACs)

Question 10

Epigenic factors associated with histone organization: histone phosphorylation

Answer 10

Occurs at Ser residues

May be associated with transcription activation or repression

Question 11

Epigenic factors associated with histone organization: effect of DNA methylation

Answer 11

Transcriptional silencing

Question 12

Difference between miRNA and IncRNA

Answer 12

miRNA leads to posttranscriptional silencing of gene expression, appear to regulate multiple protein-encoding genes

IncRNA modulates gene expression in many ways — promoting or restricting gene expression; many enhancers are sites of lncRNA synthesis

Question 13

Production of miRNAs

Answer 13

Transcription of miRNA genes produces primary mRNA which is processed by DICER, generating mature single-stranded miRNAs of 21-30 nucleotides associated with RISC

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

Question 14

Ways in which lncRNAs modulate gene expression

Answer 14

Bind to regions of chromatin and restrict RNA polymerase access

Can facilitate TF binding and thus promote gene activation

May direct DNA acetylases or methylases

Question 15

Which organelle functions in very long chain fatty acid metabolism?

Answer 15

Peroxisomes

Result in production of hydrogen peroxide

Question 16

Which organelle functions in intracellular transport and export, ingestion of extracellular substances?

Answer 16

Endosomes

Question 17

_______ = found on internal leaflet of PM, when it flips to the outside it signals apoptosis to phagocytes

Answer 17

Phosphatidylserine

Question 18

What substances pass through the PM via passive membrane diffusion?

Answer 18

Small, nonpolar molecules like O2, CO2

Steroids like estradiol, vitamin D

Water, ethanol, urea

Question 19

Caveolae-mediated endocytosis (potocytosis)

Answer 19

Noncoated plasma membrane invaginations associated with GPI-linked molecules, cAMP binding proteins, SRC-family kinases, and folate receptor

Participate in transmembrane delivery of some molecules like folate; regulation of transmembrane signaling and/or cellular adhesion via internalization of receptors and integrins

Question 20

Method for cellular uptake of LDL and transferrin

Answer 20

Receptor-mediated endocytosis

Begins at clathrin coated pit; after binding their specific receptors, LDL and transferrin are endocytosed in vesicles that fuse with lysosomes where they release their cargo (cholesterol and iron). Receptors are then recycled back to PM

Question 21

Major class of cytoskeletal proteins that form well organized bundles and networks that control cell shape and movement

Answer 21

Actin filaments

Question 22

Major class of cytoskeletal protein that imparts tensile strength and allows cells to bear mechanical stress

Answer 22

Intermediate filaments

Question 23

Major class of cytoskeletal protein that serves as connecting cables for molecules motor proteins that use ATP to move vesicles, organelles, or other molecules around cells

Answer 23

Microtubules

[kinesins are anterograde, dyneins are retrograde]

Question 24

Proteins associated with occluding (tight) junctions

Answer 24

Occludin
Claudin
Zonulin
Catenin

Question 25

Proteins associated with anchoring junctions (desmosomes)

Answer 25

Cadherins (aka E-cadherins, desmogleins, desmocollins, integrins, focal adhesion complexes)

Question 26

Lysosomal degradation can occur d/t autophagy or heterophagy. What’s the difference?

Answer 26

Autophagy = senescent organelles or denatured proteins are targeted for lysosome driven degradation by encircling them with double membrane derived from ER and marked by LC3 proteins. Triggered by cell stressors such as nutrient deprivation or certain IC infections. Heterophagy = lysosomes fuse with endosomes or phagosomes to facilitate degradation of their internalized contents. End products may be released into cytosol for nutrition or discharged into EC space

Question 27

What is the warburg effect

Answer 27

In rapidly growing cells: Glucose and glutamine serve as source of molecules used to synthesize lipids, nucleic acids, and proteins ATP generation per glucose molecule is downregulated [hallmark of cancerous cells!]

Question 28

Receptors associated with kinase activity

Answer 28

Downstream phosphorylation pathways elicited by intrinsice TK activity Examples: RTK, serine/threonine kinases, lipid kinases, nonreceptor tyrosine kinases

Question 29

_____ receptors undergo proteolytic cleavage of receptor when ligand binds, followed by nuclear translocation of cytoplasmic piece

Answer 29

Notch

Question 30

____ receptors have Wnt protein ligands and regulate IC concentrations of b-catenin (increased concentrations when ligand binds receptor and recruits ______)

Answer 30

Frizzled; disheveled

Question 31

Source and function of epidermal growth factor

Answer 31

Source: activated macrophages, salivary glands, keratinocytes Mitogenic for keratinocytes and fibroblasts; stimulates keratinocytes migration, stimulates formation of granulation tissue

Question 32

Source and function of TGF-a

Answer 32

Sources: activated macrophages, keratinocytes Stimulates proliferation of hepatocytes and many other epithelial cells

Question 33

Sources and functions of hepatocyte growth factor (scatter factor)

Answer 33

Sources: Fibroblasts, stromal cells in liver, endothelial cells Enhances proliferation of hepatocytes and other epithelial cells, increases motility

Question 34

Source and function of VEGF

Answer 34

Source: mesenchymal cells Stimulates proliferation of endothelial cells, increases vascular permeability

Question 35

Source and function of platelet-derived growth factor

Answer 35

Source: platelets, macrophages, endothelial cells Chemotactic for neutrophils, macrophages, fibroblasts, smooth muscle cells; activates and stimulates proliferation of fibroblasts, endothelial and other cells; stimulates ECM protein synth

Question 36

Sources and functions of FGF

Answer 36

Source: macrophages, mast cells, endothelial cells Chemotactic and mitogenic for fibroblasts, stimulates angiogenesis and ECM protein synthesis

Question 37

TGF-b source and function

Answer 37

Source: platelets, T cells, macrophages, endothelial cells, keratinocytes, smooth muscle cells, fibroblasts Chemotactic for leukocytes and fibroblasts; stimulates ECM protein synth, suppresses acute inflamm

Question 38

Source and function of keratinocyte growth factor

Answer 38

Source: fibroblasts Stimulates keratinocyte migration, proliferation, and differentiation

Question 39

Functions of ECM

Answer 39

Mechanical support Control of cell proliferation Scaffolding for tissue renewal Establishment of tissue microenvironments

Question 40

2 basic forms of ECM

Answer 40

Interstitial matrix — synthesized by mesenchymal cells like fibroblasts. Constituents include fibronectin, elastin, proteoglycan, hyaluronate Basement membrane — synthesized by overlying epithelium and underlying mesenchymal cells. Major constituents are type IV collagen and laminin

Question 41

3 major groups of ECM

Answer 41

Fibrous structural proteins = collagens + elastins Water-hydrated gels = proteoglycans + hyaluronan Adhesive glycoproteins = fibronectin+laminin+integrins

Question 42

2 main checkpoints of cell cycle and what regulates them

Answer 42

G1-S = monitors integrity of DNA before irreversibly committing cellular resources to DNA replication (Cyclin D-CDK4, Cyclin D-CDK6, and cyclin E-CDK2) G2-M = ensures accurate DNA replication prior to division (Cyclin B-CDK1)

Question 43

Cyclin-D-CDK proteins regulate the G1-S transition by phosphorylating the ___ protein

Answer 43

Rb

Question 44

2 families of CDKI’s

Answer 44

INK4 inhibitors = p16, p15, p18, p19 — act on D-CDK4 and D-CDK6 P21, p27, and p57 = inhibit all CDKs

Question 45

Senescence vs. quiescence

Answer 45

Senescence = no longer able to divide but still alive and metabolically active (alternative to apoptosis) Quiescence = state or period of inactivity or dormancy but can still enter cell cycle (G0)

Question 46

2 major properties of stem cells

Answer 46

Self-renewal Asymmetric division

Question 47

Major example function of long noncoding RNAs

Answer 47

X-inactivation [XIST — transcribed from X chromosome and inactivates the whole thing]

Question 48

Mature miRNAs associate with a multiprotein aggregate called the RNA-induced silencing complex (RISC). What are the 2 possible results when this complex binds with target mRNA?

Answer 48

mRNA is either degraded (perfect match) or repressed (imperfect match)

Question 49

Main difference between siRNAs and miRNAs

Answer 49

siRNAs = in vitro miRNAs = in vivo

Question 50

Proteasome = specialized type of “grinder” that selectively chews up denatured proteins and releases peptides in the process. Peptides are presented via Ag presentation in the context of ________

Answer 50

MHC Class I

Question 51

What membrane constituent can serve as a cofactor for platelets when clotting blood?

Answer 51

Phosphatidylserine

Question 52

_______ anchors may help keep the protein in on the EXTRACELLULAR leaflet of the membrane

Answer 52

GPI

Question 53

How does a small, polar molecule like alcohol cross membranes?

Answer 53

Passive diffusion

Question 54

Defects in the LDL receptor are associated with what disease?

Answer 54

Familial hypercholesterolemia

Question 55

What cell-cell process or cell-matrix interaction is involved in leukocyte extravasation?

Answer 55

Tight junctions, transcytosis (aka paracellular transport) [note that diapedesis is an example of transcytosis]

Question 56

Individual types of intermediate filaments have characteristic tissue-specific patterns of expression that can be used for assigning a cell of origin for poorly differentiated tumors. _____: nuclear lamina of all cells, maintain nuclear morphology, regulate normal nuclear transcription. Mutation leads to muscular dystrophy or progeria

Answer 56

Laminins

Question 57

Individual types of intermediate filaments have characteristic tissue-specific patterns of expression that can be used for assigning a cell of origin for poorly differentiated tumors. _______: mesenchymal cells (fibroblasts and endothelium)

Answer 57

Vimentin

Question 58

Individual types of intermediate filaments have characteristic tissue-specific patterns of expression that can be used for assigning a cell of origin for poorly differentiated tumors. _____: muscle cells; forms scaffold on which actin and myosin contract

Answer 58

Desmin

Question 59

Individual types of intermediate filaments have characteristic tissue-specific patterns of expression that can be used for assigning a cell of origin for poorly differentiated tumors. _____: glial cells around neurons; astrocytes

Answer 59

Glial fibrillary acidic protein (GFAP)

Question 60

The minus end of a microtubule is generally associated with a ______ near the nucleus where it is paired with _____

Answer 60

MTOC/centrosome; centrioles

Question 61

The ER is organized into a meshwork of tubules and flattened lamellae forming a continuous sheet around a single lumen that is topologically equivalent to the ______ environment

Answer 61

Extracellular

Question 62

What organelle is highly prominent in secretory cells like goblet or plasma cells?

Answer 62

Golgi

Question 63

Characteristic sign of atrophy

Answer 63

Autophagy

Question 64

Hallmark of autophagy

Answer 64

Decreased protein synthesis

Question 65

Mitochondria initiate protein synthesis via _______, which serves as a target for antibiotics since it leaves human translation alone

Answer 65

N-formylmethionine

Question 66

Rous Sarcoma Virus (SRC) is prototype of what type of receptor which possesses no intrinsic catalytic activity?

Answer 66

Nonreceptor tyrosine kinase (Src-family kinases)

Question 67

Frizzled family receptors are activated by Wnt protein ligands to regulate levels of _______ (second messenger in growth factor signaling), which is always targeted by ubiquitin but recruitment of ______ leads to inhibition of ubiquitin

Answer 67

beta-catenin; disheveled

Question 68

Another name for hepatocyte growth factor (HGF)

Answer 68

Scatter factor

Question 69

TGF-B causes scars and fibrosis in lungs by stimulating fibrinogen and collagen as well as inhibiting _____

Answer 69

MMPs

Question 70

Gene commonly overexpressed in breast cancers

Answer 70

ERB-B2 (HER2) [belong to EGF family and bind same receptors with intrinsic TK activity]

Question 71

Most potent inducer for VEGF production

Answer 71

Hypoxia — via HIF-1

Question 72

Increased levels of soluble version of _____ in pregnant women can lead to preeclampsia (HTN+proteinuria) by “sopping up” the free _____ required for maintaining normal endothelium

Answer 72

VEGFR-1 (s-FLT-1); VEGF

Question 73

Which types of collagen are fibrillar vs. non-fibrillar?

Answer 73

Fibrillar = Types I, II, III, and V Non-fibrillar = Types IV, IX, and VII

Question 74

What ECM components provide compressibility to tissues and serve as reservoirs for GFs secreted into the ECM like FGF and HGF?

Answer 74

Proteoglycans and hyaluronans

Question 75

_____ cells are cells that can enter the cell cycle under the right environmental stimuli _____ cells are cells that can under no circumstances enter the cell cycle Thus, the hallmark of cancer is loss of replicative ______

Answer 75

Quiescent Senescent Senescence

Question 76

Intermediate filament in nuclear lamina of all cells

Answer 76

Lamin A, B, and C

Question 77

Intermediate filament in mesenchymal cells like fibroblasts and endothelium

Answer 77

Vimentin

Question 78

Intermediate filament in muscle cells, forming the scaffold on which actin and myosin contract

Answer 78

Desmin

Question 79

Intermediate filament in axons of neurons, imparting strength and rigidity

Answer 79

Neurofilaments

Question 80

Intermediate filament in glial cells around neurons

Answer 80

Glial fibrillary acidic protein (GFAP)

Question 81

Intermediate filaments of which there are at least 30 different varities, subdivided into acidic and neutral/basic. Different types present in different cells can be used as cell markers

Answer 81

Cytokeratins