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MOD I Exam I > Chapter 1 > Flashcards

Chapter 1 Flashcards

1
Q

_______ 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.

A

Chromatids; P

Bands; interbands

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2
Q

Differentiate heterochromatin vs euchromatin

A

Heterochromatin = densely packed, transcriptionally inactive

Euchromatin = dispersed, transcriptionally active

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3
Q

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

A

Nucleosomes; histones

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4
Q

Function of nucleosome

A

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

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5
Q

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

A

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

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

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6
Q

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

A

Transposons

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7
Q

2 most common variations in the human genome

A

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

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8
Q

Epigenic factors associated with histone organization: Histone methylation

A

Occurs at Lys or Arg residues

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

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9
Q

Epigenic factors associated with histone organization: histone acetylation

A

Occurs via HATs at Lys residues

Leads to increased transcription (reversed by HDACs)

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10
Q

Epigenic factors associated with histone organization: histone phosphorylation

A

Occurs at Ser residues

May be associated with transcription activation or repression

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11
Q

Epigenic factors associated with histone organization: effect of DNA methylation

A

Transcriptional silencing

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12
Q

Difference between miRNA and IncRNA

A

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

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13
Q

Production of miRNAs

A

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

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14
Q

Ways in which lncRNAs modulate gene expression

A

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

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15
Q

Which organelle functions in very long chain fatty acid metabolism?

A

Peroxisomes

Result in production of hydrogen peroxide

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16
Q

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

A

Endosomes

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17
Q

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

A

Phosphatidylserine

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18
Q

What substances pass through the PM via passive membrane diffusion?

A

Small, nonpolar molecules like O2, CO2

Steroids like estradiol, vitamin D

Water, ethanol, urea

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19
Q

Caveolae-mediated endocytosis (potocytosis)

A

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

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20
Q

Method for cellular uptake of LDL and transferrin

A

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

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21
Q

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

A

Actin filaments

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22
Q

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

A

Intermediate filaments

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23
Q

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

A

Microtubules

[kinesins are anterograde, dyneins are retrograde]

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24
Q

Proteins associated with occluding (tight) junctions

A

Occludin
Claudin
Zonulin
Catenin

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25
Q

Proteins associated with anchoring junctions (desmosomes)

A

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

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26
Q

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

A

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

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27
Q

What is the warburg effect

A

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!]

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28
Q

Receptors associated with kinase activity

A

Downstream phosphorylation pathways elicited by intrinsice TK activity

Examples: RTK, serine/threonine kinases, lipid kinases, nonreceptor tyrosine kinases

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29
Q

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

A

Notch

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30
Q

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

A

Frizzled; disheveled

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31
Q

Source and function of epidermal growth factor

A

Source: activated macrophages, salivary glands, keratinocytes

Mitogenic for keratinocytes and fibroblasts; stimulates keratinocytes migration, stimulates formation of granulation tissue

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32
Q

Source and function of TGF-a

A

Sources: activated macrophages, keratinocytes

Stimulates proliferation of hepatocytes and many other epithelial cells

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33
Q

Sources and functions of hepatocyte growth factor (scatter factor)

A

Sources: Fibroblasts, stromal cells in liver, endothelial cells

Enhances proliferation of hepatocytes and other epithelial cells, increases motility

34
Q

Source and function of VEGF

A

Source: mesenchymal cells

Stimulates proliferation of endothelial cells, increases vascular permeability

35
Q

Source and function of platelet-derived growth factor

A

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

36
Q

Sources and functions of FGF

A

Source: macrophages, mast cells, endothelial cells

Chemotactic and mitogenic for fibroblasts, stimulates angiogenesis and ECM protein synthesis

37
Q

TGF-b source and function

A

Source: platelets, T cells, macrophages, endothelial cells, keratinocytes, smooth muscle cells, fibroblasts

Chemotactic for leukocytes and fibroblasts; stimulates ECM protein synth, suppresses acute inflamm

38
Q

Source and function of keratinocyte growth factor

A

Source: fibroblasts

Stimulates keratinocyte migration, proliferation, and differentiation

39
Q

Functions of ECM

A

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

40
Q

2 basic forms of ECM

A

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

41
Q

3 major groups of ECM

A

Fibrous structural proteins = collagens + elastins

Water-hydrated gels = proteoglycans + hyaluronan

Adhesive glycoproteins = fibronectin+laminin+integrins

42
Q

2 main checkpoints of cell cycle and what regulates them

A

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)

43
Q

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

A

Rb

44
Q

2 families of CDKI’s

A

INK4 inhibitors = p16, p15, p18, p19 — act on D-CDK4 and D-CDK6

P21, p27, and p57 = inhibit all CDKs

45
Q

Senescence vs. quiescence

A

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)

46
Q

2 major properties of stem cells

A

Self-renewal

Asymmetric division

47
Q

Major example function of long noncoding RNAs

A

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

48
Q

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?

A

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

49
Q

Main difference between siRNAs and miRNAs

A

siRNAs = in vitro

miRNAs = in vivo

50
Q

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 ________

A

MHC Class I

51
Q

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

A

Phosphatidylserine

52
Q

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

A

GPI

53
Q

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

A

Passive diffusion

54
Q

Defects in the LDL receptor are associated with what disease?

A

Familial hypercholesterolemia

55
Q

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

A

Tight junctions, transcytosis (aka paracellular transport)

[note that diapedesis is an example of transcytosis]

56
Q

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

A

Laminins

57
Q

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)

A

Vimentin

58
Q

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

A

Desmin

59
Q

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

A

Glial fibrillary acidic protein (GFAP)

60
Q

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

A

MTOC/centrosome; centrioles

61
Q

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

A

Extracellular

62
Q

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

A

Golgi

63
Q

Characteristic sign of atrophy

A

Autophagy

64
Q

Hallmark of autophagy

A

Decreased protein synthesis

65
Q

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

A

N-formylmethionine

66
Q

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

A

Nonreceptor tyrosine kinase (Src-family kinases)

67
Q

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

A

beta-catenin; disheveled

68
Q

Another name for hepatocyte growth factor (HGF)

A

Scatter factor

69
Q

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

A

MMPs

70
Q

Gene commonly overexpressed in breast cancers

A

ERB-B2 (HER2)

[belong to EGF family and bind same receptors with intrinsic TK activity]

71
Q

Most potent inducer for VEGF production

A

Hypoxia — via HIF-1

72
Q

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

A

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

73
Q

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

A

Fibrillar = Types I, II, III, and V

Non-fibrillar = Types IV, IX, and VII

74
Q

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

A

Proteoglycans and hyaluronans

75
Q

_____ 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 ______

A

Quiescent

Senescent

Senescence

76
Q

Intermediate filament in nuclear lamina of all cells

A

Lamin A, B, and C

77
Q

Intermediate filament in mesenchymal cells like fibroblasts and endothelium

A

Vimentin

78
Q

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

A

Desmin

79
Q

Intermediate filament in axons of neurons, imparting strength and rigidity

A

Neurofilaments

80
Q

Intermediate filament in glial cells around neurons

A

Glial fibrillary acidic protein (GFAP)

81
Q

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

A

Cytokeratins

MOD I Exam I (5 decks)

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