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Molecular Genetics > Final Exam > Flashcards

Final Exam Flashcards

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1
Q

Nematode Aging

A

LET-363 and Target of rapamycin promote aging

Daf-2 and insulin/IGF-1 receptor to daf-16/FOXO stop aging

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2
Q

Fruit Fly Aging

A

Target of rapamycin promotes aging

dINR and insulin/IGF-1 receptor to dFOXO stop aging

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3
Q

Mouse Aging

A

Target of rapamycin promotes aging

Growth of hormone to IGF-1, IGF-1 receptor and insulin receptor to FOXO1 and FOXO3 stop aging

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4
Q

RNA interference (RNAi)

A

Post-transcription gene silencing; double-stranded RNA (when introduced into a cell) causes sequencing-specific degradation of homologous mRNA sequences

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5
Q

Argonaute

A

One of the main components in RISC; cleaves and discards the passenger strand of the siRNA duplex leading to activation of the RISC

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6
Q

Dicer

A

RNAase 3 enzyme

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7
Q

siRNA

A

21-23 nt short interfering RNA

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8
Q

RISC

A

RNA-inducing silencing complex

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9
Q

ER stress

A

Physiological and pathological stimuli disrupt the ER homeostasis, resulting in midfielder and unfolded proteins

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10
Q

Unfolded Protein Response (UPR)

A

ER stress activated complex signaling network to reduce ER stress and restore the ER homeostasis

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11
Q

Three aims of UPR

A

1) restore normal function of cell by stopping protein translation
2) degrading midfielder proteins
3) activating signaling pathways that increase the production of molecular chaperones in protein folding

If not achieved, UPR aims towards apoptosis

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12
Q

BIP

A

Immunoglobin biding protein

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13
Q

ATF6

A

Activating Transcription Factor 6

Not required for longevity phenotype of daf-2 mutants

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14
Q

XBP1

A

X-box binding protein 1

New ER stress response, longevity genes leads to improved ER homeostasis

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15
Q

PERK

A

PKR-like ER kinase

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16
Q

IRE1

A

Inositol Requiring 1

Required for longevity phenotype of daf-2 mutants

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17
Q

ERAD

A

ER-associated protein degradation

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18
Q

Pek-1

A

Not required for longevity phenotype of daf-2 mutants

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19
Q

Sir-2 and daf-16

A

Sir2 stimulates daf-16 activity to increase worm survival

14-3-3 and sir2 are required for daf-16 to function

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20
Q

RAS Signal Pathway components

A

SOS, GAP, ERK, RAF, MEK, FOS

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21
Q

SOS

A

Guanine nucleotide exchange factor (first in pathway)

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22
Q

GAP

A

GTPase activating protein (after SOS)

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23
Q

ERK

A

Extracellular signal-regulated kinases

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24
Q

RAF, MEK, ERK

A

Protein kinase phosphorilation cascade (follows GAP)

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25
FOS
Transcription factor Cell proliferation, differentiation, and survival (end of pathway)
26
Inhibition of RAS
Extends fly lifespan RAS dominate negative mutants
27
MEK inhibitor and what it does
Trametinib Extends fly lifespan
28
Trametinib
MEK inhibitor; approved for use with dabrafenib for untraceable/metastatic melanoma with BRAF mutation
29
14-3-3 protein name
Name refers to elution and migration pattern of proteins on DEAE-cellulose chromatography and starch-gel electrophoresis
30
14-3-3 ability
Ability to bind a multitude of functionally diverse Signaling proteins Includes kinases, phosphatases, and transmembrane receptors
31
What 14-3-3 does
14-3-3 binding variably regulates its partners, ranging from positive to negative regulation via several different mechanisms Bonds specific phosphoserine/threonine motifs on the target protein
32
14-3-3 First major mode of action
binding can alter ability to target protein to interact with other proteins (bind with IRS-1 attenuated ability to recruit and activate PI-3 kinase)
33
14-3-3 second major mode of action
Binding can modify the target protein localization which causes its target’s exclusion from the nucleus and it’s retention in the cytoplasm
34
14-3-3 third major mode of action
Can bridge two proteins together, serving as a phosphorylation dependent scaffold protein
35
14-3-3 forth major mode of action
Binding can alter the intrinsic catalytic activity of the target protein, inhibit or augment it’s function
36
14-3-3 fifth major mode of action
Binding can protect the target protein from other modifications such as dephosphorylation and proteolysis
37
Sirtuin (or Sir2 proteins)
Sir2 - silent information regulation 2 Required for lifespan extension resulted from glucose restriction in yeast cells Are protein deacetylases dependent on nicotine adenine dinucleotide (NAD) and are found in organisms ranging from Baxter to humans Various enzyme activities (mono-ribosyltransferase and deacylase)
38
Overexpression of Sir2
Extends lifespan of C. elegans, Drosophila, and mouse In C. elegans, promotes nuclear localization of DAF-16/FOXO transcription factor
39
Saccharomyces cerevisiae, three different kinds of loci subject to gene silencing
Silent mating-type loci, telomeric regions, rDNA repeats
40
Accumulation of rDNA circles; Extrachromosomal rDNA circle (ERC)
A young cell — excision/inheritance of ERC — replication, recombination, asymmetrical segregation (can repeat this step) — old cell, nucleolar fragmentation, death
41
Deacylase activity
Important for lifespan regulation Depends on NAD level, which links it’s enzymatic activity directly to energy status of cell via cellular NAD:NADH ratio
42
Nicotinamide adenine dinuleotide (NAD)
Extends C. elegans lifespan
43
What does Sirtuins (NAD+ dependent deacetylases) do
Remove acetyl groups from lysine residues within proteins in the presence of NAD+
44
Yeast Sir2
A histone deacetylase
45
Sir2 enzyme activity results
Results in tighter packaging of chromatin and a reduction in transcription at the targeted gene locus: telomeric sequences, the hidden MAT loci (HM loci) and the ribosomal DNA locus
46
Seven sirtuins in mammals
Sirt1 - homologous of Sir2, overexpression mimics diet restriction Sirt2 - mainly expressed in brain Sirt3, Sirt4, Sirt5 - active in mitochondria Sirt6 and Sirt7 - active in nucleus of cell
47
Overexpression of sirt6
Decreases level of phosphorylated AKT Decreases level of phosphorylated FOXO and S6K INCREASES LONGEVITY OF MALE MICE - reduces IGF signaling pathway in white adipose tissue
48
Resveratrol
Red wine
49
Sirt1 activator SRT1720
Extends lifespan and improves health of mice fed standard diet
50
What does Resveratrol do
Improves health and survival of mice in a high-caloric diet
51
Autophagy definition
A catabolic process involving degradation of a cell’s own components through the lysosomal machinery
52
Autophagy: first type
Chaperone-mediated: a cytosolic chaperone protein recognizes and binds proteins to form a substrate-chaperone complex delivered to the lysosome through lysosome-associated membrane protein (LAMP) type 2A
53
Autophagy: second type
Microautophagy: a direct engulfment if cellular components by invagination of the lysosomal member
54
Autophagy: third type
Macroautophagy: process in which cytosol and organelles are sequestered within double-membrane vesicles that deliver the contents to the lysosome/vacuole for degradation and recycling of the resulting macromolecules
55
Biological functions of autophagy
``` Survival during starvation anti-aging differentiation and development protection against neurodegeneration innate immunity cell growth control/tumor suppression cell death ```
56
When does autophagy occur
Misfolded protein goes to phagosomes/lysosomes, which goes to autophagy
57
Telomere definition
A region of repetitive nucleotide sequences at the end of a chromosome, which protects the end of the chromosome from deterioration or from fusion with neighboring chromosomes
58
About telomere
Shorten with each cell division | Estimated that human telomere lose about 100 base pairs from their telomeric DNA at each mitosis
59
Cellular senescence
Triggered when telomere are on average 4-6 kb
60
Telomere Hypothesis of Aging
Telomeres shorten with age (tissue with high cell turnover); therefore, telomere shortening is a cause of aging
61
Telomerase definition
An enzyme that adds telomere repeat sequences to the 3’ end of DNA strands Reverse transcriptase that carries its own RNA molecule, used as a template when it elongates telomeres
62
Long telomeric DNA
Long lifespan in worms
63
p53
Guardian of the genome Cell cycle arrest — DNA repair — cell cycle restart — cellular and genetic stability Apoptosis — death and elimination of damaged cells — cellular and genetic stability
64
Progeria / Hutchinson-Gilford Progeria Syndrome (HGPS)
Extremely rare genetic condition wherein symptoms resembling aspects of aging are manifested at an early age 1 per 8 million live births Diseased live to mid teens and early twenties; occurs as a new mutation and is rarely inherited
65
Werner syndrome
An autosomal recessive disorder. WRN gene associated with this syndrome lies on chromosome 8 and it’s the only gene known to be associated with Werner syndrome. Caused by mutation in the WRN gene which codes a DNA helicase that functions 3’ to 5’
66
What is observed in Werner syndrome
Increase telomere attrition and genomic instability Rapid telomere decay is thought to play a causal role in the clinical and pathological manifestations of the disease

Molecular Genetics (1 decks)

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