Functions and Dysfunctions of Genomic Regulation

Question 1

Purines

Answer 1

Adenosine and Guanine

Question 2

Pyrimidines

Answer 2

Cytosine and Thymine

Question 3

How many bonds between A and T

Answer 3

2

Question 4

How many bonds between G and C

Answer 4

3

Question 5

What is double stranded and anti-parallel

Answer 5

DNA

Question 6

What are he basic unit of chromosome packing

Answer 6

Nucleosomes

Question 7

Euchromatin

Answer 7

Lightly packed form of chromatin (DNA, RNA, and protein).

• Highly enriched in genes
• often (but not always) under active transcription
• most active protein of genome
• abouT 92% OF HUMAN GENOME IS EUCHROMATIC
• remainder is heterochromatin

Question 8

Heterochromatin

Answer 8

Very condensed chromatin-stains darkly throughout the cell cycle, even in interphase

• thought to be late replicating and genetically inactive
• highly concentrated at centromers and telomers
• contains VERY FEW ACTIVE GENES

Question 9

What is the position effect

Answer 9

Activity of a gene depend on relative position on chromosone

Question 10

Will genes be actively espresses or silenced if located near heterochromatin

Answer 10

silenced

Question 11

What information is found on chromosomes?

Answer 11

Genes - encoding proteins, encoding RNA molecules

-Reg information, “JUNK” DNA

Question 12

How many chromosomes in the human genome

Answer 12

46, 2 pairs of 23.

Question 13

What was the human genome project

Answer 13

sequence of the human genome. 3 billion nucleotides

Question 14

How many genes in the human genome

Answer 14

26,000

Question 15

What percent of the genome is responsible for codine

Answer 15

1.5 percent (in exons)

Question 16

What do introns usually begin with and what do they end with?

Answer 16

[…GT] and end with [AG…]

Question 17

Does histone deacetylation actively repress or promote gene expression

Answer 17

histone deacetylation actively represses gene expression

Question 18

Does histone acetylation actively repress or promote gene expression

Answer 18

Histome acetylation actively promotes gene expression

Question 19

What are types of PTMs on histone tails

Answer 19

Methylation
acetylation
phosphorylation
ubiquitination
SUMOylation
Citrullination
ADP-ribosylation

Question 20

DNA Methylation

Answer 20

Methyl groups are added to the DNA molecule (C and A) by METHYL TRANSFERASE enzymes.

• represses gene transcription when at gene promoter
• Essential for normal development

Question 21

What does DNA methylation change without changing the DNA sequence.

Answer 21

Methylation changes the activity of the DNA segment

Question 22

What is DNA methylation essential for?

Answer 22

Genomic imprinting

• x-xhromosome inactivation
• repression of transposable elements
• aging
• carcinogenesis

Question 23

What are alterations of DNA methylation an important of

Answer 23

cancer development

Question 24

What is hypomethylation associated with

Answer 24

• chromosomal instability

- loss of imprinting

Question 25

What is hypermethylation associated with

Answer 25

- gene promoters | - might be target for epigenetic therapy

Question 26

Which direction does DNA Polymerase synthesize new DNA

Answer 26

from 5' to 3'

Question 27

What does DNA Polymerase need to begin processing

Answer 27

a primer with a free 3' -OH

Question 28

What is DNA Helicase and what does it do?

Answer 28

DNA Helicase unwinds DNA - it is a protein with 6 identical subunits - binds and hydrolyzes ATP - Conformational change - propels it like a rotary engine - passing through a center hole - pries apart the helix (1000, BP/sec)

Question 29

Single-Stranded DNA-Binding Protein (SSBP)

Answer 29

``` Binds Cooperatively to Exposed ssDNA (Straightens the chain) -helps stabilize the unwound DNA -Prevents the formation of hairpins -DNA bases remain exposed ```

Question 30

DNA Topoisomerase

Answer 30

Relieves overwound supercoils (every 10bp corresponds to one turn) - reversible enzyme - breaks a phosphodiester bond - changes superhelicity - relieves supercoiling * PHARMA DRUGS THAT TARGET TOPOISOMERASE ARE ANTI CANCER

Question 31

Irinotecan

Answer 31

Topoisomerase I inhibitor used to treat colorectal cancer

Question 32

Etoposisde, Anthracylines

Answer 32

Topoisomerase II inhibitor - etoposide causes secondary leukemias - anthracyclines cause cardiotoxicity

Question 33

Why are topoisomerases used as anticancer drugs

Answer 33

they block the cell cycle they generate single and double stranded breaks they harm the integrity of the genome they lead to apoptosis and cancer cell death

Question 34

How can UV radiation cause DNA damage

Answer 34

UV radiation from sun can produce a covalent linkage between two adjacent pyrimidines (T-T or C-T) -pyrimidine dimers

Question 35

Spontaneous DNA damage

Answer 35

Depurination and deamination

Question 36

Outcomes of spontaneous DNA damage

Answer 36

- DNA replication occurs | - Base deletion or substitution

Question 37

Cross Linking agens

Answer 37

- Nitrogen mustard - cisplatin - Mitomycin C - Carmustine

Question 38

Alkylating Agents

Answer 38

``` Dimethyl sulfate (DMS) Methyl methanesulfonate (MMS) ```

Question 39

Alkylating Agents

Answer 39

``` Dimethyl sulfate (DMS) Methyl methanesulfonate (MMS) ```

Question 40

Intercalacting agents

Answer 40

Thalidomide

Question 41

Direct Repair (enzyme repair)

Answer 41

Photolyase enzyme repairs pyrimidine dimers

Question 42

Base exclusion repair (BER)

Answer 42

single-base mismatches-DNA glycolases

Question 43

Nucleotide excision repair

Answer 43

-Xeroderma pigmentosum

Question 44

Mismatch exclusion repair (MER)

Answer 44

mismatched base in daughter strand | -Hereditary nonpolyposis colorectal cancers

Question 45

recombination repair - nonhomologous end joining - homologous recombination

Answer 45

double strand breaks, interstrand cross-linking | -BRCA1/2 breast cancer

Question 46

Transcription-coupled repair (TCR)

Answer 46

stalled RNA polymerase during transcription (not replication) -Cockayne syndrome

Question 47

Transcription-coupled repair (TCR)

Answer 47

stalled RNA polymerase during transcription (not replication) -Cockayne syndrome

Question 48

What are the three Post-translational modification (PTM) regulated cellular events

Answer 48

- protein biological activities - subcellular ocalization - degredation/stability

Question 49

Types of reversible PTMs on proteins

Answer 49

- phosphorylation - acetylation - ubiquitination - SUMOylation - methylation

Question 50

What is the start of translation initiating methionine

Answer 50

ATG

Question 51

DNA methylation in Humans

Answer 51

- occurs at the 5 position of the pyrimidine ring of the cytosine residues - occurs within CpG sites - Forms 5-methylcytosines - multiple methylated CpG sites in CpG islands of promoters STABLY SILENCES GENES

Question 52

Where is ubiquitin attached to on target cells

Answer 52

lysine residues