Functions and Dysfunction in Genomic Regulation

Question 1

DNA and histone interactions

Answer 1

Negatively charged DNA backbone is wound around positively charged histones. K residues in histones are the target of PTMs.

Question 2

Nucleosome

Answer 2

Basic unit of chromosomal packaging. Includes a core of 8 histone proteins.

Question 3

Chromatin

Answer 3

Protein + DNA = Chromatin

“Beads on a string.”

Question 4

Euchromatin

Answer 4

Lightly packed chromatin that is highly expressed. Often under active transcription. Approximately 92% of genome is euchromatin.

Question 5

Heterochromatin

Answer 5

Very tightly packed chromatin. Highly concentrated at centromeres and telomeres.

Question 6

1953

Answer 6

Watson and Crick describe the double helix structure of DNA.

Question 7

1966

Answer 7

Nirenburg, Khorana and Holley determine the genetic code.

Question 8

CGH arrays

Answer 8

Detects copy number variation in genome. Human genome is probed with a chip from one person and a “normal” reference.

Question 9

RNAi

Answer 9

miRNA molecules inhibit gene expression or translation - neutralizes mRNA molecules.

Question 10

Long terminal repeats (LTRs)

Answer 10

Identical sequences of DNA that are found at either end of retroposons formed by reverse transcription of retroviral RNA. Viruses use it to insert their genetic material into the host genome.

Question 11

Histone acetylation

Answer 11

Highly acetylated histones are more active, causing the chromatin to loosen.

Question 12

HDAC and HAT

Answer 12

HDAC - deacetylates histones.

HAT - acetylates histones.

Question 13

DNA methylation

Answer 13

Methyl groups added to C and A by methyl transferase. Represses gene transcription when at the promoter.

Question 14

CpG islands

Answer 14

Areas of high concentration of C and G. Located at or near the transcriptional start site.

Question 15

CpG islands and cancer

Answer 15

CpG islands acquire abnormal hypermethylation, silencing transcription. Can be inherited by daughter cells.

Question 16

Hypomethylation

Answer 16

Causes chromosomal instability and loss of imprinting.

Question 17

Hypermethylation

Answer 17

Associated with gene promoters. Can arise secondary to gene silencing. Possible target for epigenetic therapy.

Question 18

Proteins/enzymes involved in DNA replication (5)

Answer 18

1. DNA helicase - unwinds DNA using ATP. Has 6 identical subunits.
2. Topoisomerase - relieves tension.
3. DNA pol - synthesizes the DNA.
4. SSBPs - binds to ssDNA to prevent hairpin fomration and stabilize unwound DNA.

Question 19

Topoisomerase inhibitors as anti-cancer agents

Answer 19

Blocks the cell cycle, generates single and double stranded breaks. Harms the integrity of the genome and leads to apoptosis and cancer cell death.

Question 20

Pyrimidine dimers

Answer 20

Caused by UV radiation. Covalent linkage forms between T-T or T-C.

Question 21

Spontaneous DNA damage (2)

Answer 21

1. Depurination: 5,000 purines lost a day

2. Deamination: C to U changes 100 bases/day

Question 22

Transcription-coupled repair

Answer 22

Cells can preferentialy direct DNA repair to sequence that are being highly expressed by linking RNA pol. It is specific for the strand being transcribed.

Question 23

Cockayne’s syndrome

Answer 23

Defect in transcription-coupled repair. Causes growth retardation, MSK abnormalities and sensitivity to sunlight. RNA pol is stalled at the sites of damage in important genes.

Question 24

DNA methylation in humans

Answer 24

Occurs at 5 position of ring in C residues withing CpG sites. Fors 5-methylcytosines that can stably silence genes.

Question 25

Ubiquitin

Answer 25

Tags proteins for degredation. Exists in all euk cells and is attached to K residues on target proteins. Protein degraded by proteasome.