Gene Expression, Mitosis, & Diseases

Question 1

What are the two main mechanisms used to control gene expression?

Answer 1

DNA control elements (cis) & transcriptional activators/suppressors (trans)

Question 2

What is the TATA box on DNA?

Answer 2

A promoter that is a bit upstream of transcription start; determines site of transcription initiation and directs binding of RNA Pol II

Question 3

What is a promoter proximal element?

Answer 3

Further upstream of start site of transcription than is the TATA box; helps regulate transcription & can be cell type specific

Question 4

What is an enhancer?

Answer 4

An enhancer contains many control elements. It is very upstream or downstream to start site of transcription

Question 5

Thalassemias, Hemophilia B-leyden, and Fragile X-Syndrome are associated with mutations in what?

Answer 5

DNA control elements

Question 6

Describe Thalassemias

Answer 6

An anemia associated with slicing mutations of genes. Also due to mutations in betaglobin gene

Question 7

Describe Hemophilia B-leyden

Answer 7

An X-linked clotting disorder in which only 1% of normal factor 9 is made

Question 8

Describe Fragile X-Syndrome

Answer 8

An X-linked defect in a control element called efemar which controls a protein that transports mRNAs and synapes; frequent cause of mental retardation

Question 9

Transcriptional activators are composed of which distinct functional domains?

Answer 9

DNA-binding domain, activation domain, flexible protein domain

Question 10

DNA-Binding domains of transcriptional activators fall into which four classes?

Answer 10

Homeodomain structure, zinc-finger, basic leaucin zipper (bZIP), & helix-loop-helix

Question 11

Describe craniosynostosis

Answer 11

A disease in which the cranial bones fuse prematurely. This is caused when a small defect in a homeodomain protein MSX2 causes it to bind DNA more tightly, resulting in a gain-of-function

Question 12

A damage in the homeodomain protein MSX2 is associated with which abnormality?

Answer 12

Craniosynostosis

Question 13

Describe Androgen Insensitivity Syndrome

Answer 13

A mutation in the DNA-binding or ligand binding domain of the androgen protein (zinc finger) causes the androgen receptor to be less responsive to androgen

Question 14

Describe Waardenburg Syndrome Type II

Answer 14

~15% of cases result from a mutation in MITF gene - affects transcription of genes important in pigmentation and hearing

Question 15

Which types of transcriptional activators can form dimers?

Answer 15

bZIP, helix-loop-helix, & zinc finger

Question 16

What is the benefit of dimerizing transcriptional activators together?

Answer 16

Combinatorial Control! If each activator recognizes a specific DNA sequence, then combining multiple allows for more transcriptional control.

Question 17

What is the function of activation domains of transcriptional activators?

Answer 17

To recruit coactivators and general transcription machinery

Question 18

Describe the structure of chromatin

Answer 18

The fundamental repeating unit of chromatin is the nucleosome, which contains DNA wrapped around an octomer of histone proteins

Question 19

Describe ATP-dependent chromatin remodelers

Answer 19

Using ATP hydrolysis, the histone-DNA contact is broke in order to slide the histone along the DNA to uncover an area of DNA.

Question 20

What is the main site of post-translational histone modification?

Answer 20

Unstructured tails of histones

Question 21

What do histone acetyl transferases (HATs) do?

Answer 21

They hyperacetylate histone lysine N-terminal tails, neutralizing the charge and allowing the chromatin to “open up” and make room for transcription.

Question 22

What do histone deacetylases (HDACs) do?

Answer 22

HDACs deacetylate histone N-terminal tails to tight up chromatin and repress transcription

Question 23

Do activators or repressors recruit HATs? HDACs?

Answer 23

Activators recruit HATs and repressors recruit HDACs

Question 24

Describe Rubinstein-Taybi Syndrome

Answer 24

Results from CBP haploinsufficiency; CBP is a co-activator for transcription factors; has HAT activity; may affect transcription of multiple gene targets

Question 25

What is euchromatin?

Answer 25

Where genes reside; the more accessible form of chromatin

Question 26

What is heterochromatin?

Answer 26

The part of chromatin that is always repressed because the DNA is inaccessible (found at centromeres, telomeres, and some internal chromosome positions)

Question 27

What is the difference between constitutive heterochromatin and facultative heterochromatin

Answer 27

Constitutive heterochromatin is permanently heterochromatin and contains satellite DNA. Facultative heterochromatin can change to euchromatin, depending on cell type or developmental stage, and is enriched in LINE sequences.

Question 28

What are the three domains of nuclear receptors?

Answer 28

Variable region, DNA-binding domain, Hormone-binding domain

Question 29

Estrogen induces transcriptional (activation/repression) through ER by causing its _________.

Answer 29

Activation; Dimerization

Question 30

How does Tamoxifen antagonize estrogen?

Answer 30

It binds to ER and prevents recruitment of HAT co-factors

Question 31

What are some ways we regulate the trans-acting factors themselves? (#5)

Answer 31

1. Controlling protein conformation by binding a ligand 2. Regulating entry into nucleus 3. Regulating amount of transcription factor in the cell 4. Regulating binding to DNA 5. Phosphorylation of DNA-binding protein alters properties

Question 32

How do Id proteins negatively regulate DNA binding of bHLH proteins?

Answer 32

Heterodimerizing through their HLH domains but preventing DNA binding due to their lack of a basic domain

Question 33

What is the culprit protein of Alzheimer's?

Answer 33

Amyloid beta42

Question 34

What is responsible for extracellular cleavage of beta-amyloid precursor protein (APP)?

Answer 34

alpha-secretase or beta-secretase

Question 35

What is responsible for transmembrane cleavage of beta-amyloid precursor protein (APP)?

Answer 35

gamma-secretase

Question 36

What is the phenotype of a gene defect of beta-amyloid precursor protein mutations on chromosome ____?

Answer 36

Increased production of beta-amyloid proteins of beta-amyloid protein 42; 21

Question 37

What is the phenotype of a gene defect of apolipoprotein E4 polymorphism on chromosome ____?

Answer 37

Increased density of beta-amyloid plaques and vascular deposits; 19

Question 38

What is the phenotype of a gene defect of Presenilin 1 mutations of chromosome ____?

Answer 38

Increased production of beta-amyloid protein 42; 14

Question 39

What is the phenotype of a gene defect of Presenilin 2 mutations of chromosome ____?

Answer 39

Increased production of beta-amyloid protein 42; 1

Question 40

What are three medications used to help treat Alzheimer's symptoms?

Answer 40

NSAIDs, memantine, donepezil

Question 41

Prion protein is the product of which chromosomal gene?

Answer 41

PRNP

Question 42

PrP(c) is the normal prion protein. Which is the diseased protein?

Answer 42

PrP(Sc)

Question 43

What is the annual incidence of Prion disease?

Answer 43

~300

Question 44

CDK needs to be bound to what for it to be activated?

Answer 44

Cyclin

Question 45

RB (retinoblastoma protein) is an ____________ of the cell cycle. It is inhibited by ________________.

Answer 45

inhibitor; CDK phosphorylation

Question 46

What is RB attached to when it is active, and releases when it is phosphorylated by CDK?

Answer 46

E2F (transcription factor)

Question 47

What are the two classes of CDIs (CDK inhibitors)?

Answer 47

Ink4 (p15, p16, p18, p19) & Cip/Kip (p21, p27, p57_

Question 48

Which CDI is frequently mutated in cancer?

Answer 48

p21

Question 49

Ink4 family of CDIs is specific to kinases that bind to _________.

Answer 49

cycD family

Question 50

Cip/Kip CDIs are specific to kinases that bind to __________.

Answer 50

Cyc A, B, C, D, E families (non-specific)

Question 51

What does APC (anaphase promotion complex) do?

Answer 51

Inactivates Cdk

Question 52

Rad17 binds directly to DNA damage and induces what else?

Answer 52

ATM & ATR, which activate p53 and p21 which inhibit CDK and halt cell cycle.

Question 53

Name two pathways to repair DNA double strand breaks

Answer 53

Non-homologous end joining (NHEJ) and homologous recombination (HR)

Question 54

How does NHEJ work?

Answer 54

With recognition of the DS break by Ku -> Ku recruits DNA-PKcs -> nuclease removes damaged DNA and polymerase fills gap -> ligase restores phosphodiester backbone on both strands