Genomic Regulation

Question 1

euchromatin

Answer 1

Lightly packed form of chromatin- (DNA, RNA and protein)
 Highly enriched in genes
 Often (but not always) under active transcription
 Most active portion of the genome
 Approximately 92% of the human genome is euchromatic

Question 2

heterchromatin

Answer 2

condensed –> Stains darkly throughout the cell cycle, even in interphase
Thought to be late replicating and genetically inactive
Highly concentrated at centromeres and telomeres
Contains very few active genes:
Those that are present are resistant to gene expression

Question 3

position effect

Answer 3

Activity a gene depends on relative position on chromosome:

 Actively expressed genes will be silenced if relocated near heterochromatin

Question 4

copy number variations detection

Answer 4

Comparative Genome HybridizationProbe Human Genome CHIP with DNA from one
person and with DNA from a ‘normal’ reference DNA
- can detect deletions of genes

Question 5

long terminal repeats

Answer 5

 Repeat hundreds or thousands of times
 Found at either end of retrotransposons (proviral DNA)
 Formed by reverse transcription of retroviral RNA
 Used by viruses to insert their genetic material into the host genomes

Question 6

Histone Deacetylation

Answer 6

Actively Represses Gene Expression
compressed via HDACs (Histone Deacetylases)

opposed by Histone Acetyl
Transferase (HAT)

Question 7

DNA methylation

Answer 7

methylate cytosine + adenine
–> At gene promotor –> Represses transcription

associated with: 
 - Genomic imprinting
• X-chromosome inactivation
• Repression of transposable elements
• Aging
• Carcinogenesis

Question 8

Hypomethylation

Answer 8

• -> Chromosomal instability

- -> Loss of imprinting

Question 9

Hypermethylation

Answer 9

• Associated with gene promoters
  –> Can arise secondary to gene (oncogene suppressor) silencing
  • Might be a target for epigenetic therapy

Question 10

Direction of DNA synthesis

Answer 10

DNA-dependent DNA polymerase
5’ –> 3’

• requires a primer with a free 3’ -OH to begin

Question 11

DNA helicase

Answer 11

unwinds DNA Protein with 6 identical subunits
Bind and hydrolyze ATP –> Conformational change
Propels it like a rotary engine
Passing through a center hole

Question 12

DNA Topoisomerase

Answer 12

Reversible enzyme
• Breaks a phosphodiester bond
• Changes superhelicity
• Relieves supercoiling

anti-cancer agents target this!
–> Block the cell cycle
• Generate single and double stranded breaks
• Harms the integrity of the genome
• Leads to apoptosis and cancer cell death

Question 13

UV radiation DNA damage

Answer 13

produce a covalent linkage between two adjacent pyrimidines (T-T or C-T)
• Pyrimidine dimers

Question 14

non-ionizing radiation

Answer 14

bases bond (thymine-thymine)

Question 15

ionizing radiation

Answer 15

DNA protein crosslinks are induced

ex: thymine-tyrosine bind

Question 16

spontaneous DNA damage

Answer 16

–> Depurination: 5000 purine lost, bases/day
–> Base deletion or substitution
–> Deamination:
adenine –> hypoxanthine
guanine –> xanthine
cytosine –> uracil

Question 17

Why are Methylated Cytosine Residues in CpG Sites/Islands problematic?

Answer 17

CpG Sites/ CpG Islands (Adjacent Cytosine-Phophate-Guanine)
 Associated with inactive genes
 T mismatches with G
 Methylation of CpG islands stably silences genes (Cancer/DNA Repair Genes)

Question 18

Cross-linking chemical agents

Answer 18

prevents DNA replication and transcription 
nitrogen mustard
cisplatin
mitomycin C 
carmustine

Question 19

alkylating agents

Answer 19

attach akyl group 
dimethy sulfate (DMS)
methyl methanesulfonate (MMS)

Question 20

intercalating agents

Answer 20

insert into DNA b/t pairs -> unwinding, separation of bps 
ethidium bromide 
**thalidomide 
doxorubicin
daunomycin

Question 21

deamination

Answer 21

adenine -> hypoxanthine
guanine -> xanthine
cytosine -> uracil

Question 22

ionizing damage

Answer 22

strand breaks
modify bases
DNA-ptn crosslinks

*recombination repair

Question 23

nonionizing DNA damage

Answer 23

thymine dimers
covalent linkage b/t adjacent pyrimidines (T-T)

• direct repair
• nucleotide-excision repair

Question 24

base-excision repair

Answer 24

single base mismatches
small non-distorting alterations
depurination

altered base flipped out
detected by DNA glycosylases 
endonuclease cleaves bond 
lyase removes phosphate 
DNA pol adds correct nt 
ligase

Question 25

nucleotide excision repair

Answer 25

chemical adducts -> distort DNA
pyrimidine dimers
BPDE-guanine adducts
cisplatin adducts

NER complex recognizes distortion
create nicks, remove stretch
DNA pol, ligase

Question 26

mismatch excision repair

Answer 26

mismatched base in daughter strand

MER complex (detects error) 
helicase/endonuclease (cuts out wrong base) 
DNA pol, ligase