Functions and Dysfunctions of Genomic Regulation Flashcards Preview

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Flashcards in Functions and Dysfunctions of Genomic Regulation Deck (55)
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1
Q

How does histone protein bind to DNA?

A

Hydrophobic Interactions and Salt Linkages

~20% of histone protein amino acid residues are Lysine (Lys) or Arginine (Arg).

Positive charges bind to negative backbone of DNA

2
Q

Proteins that bind to DNA are divided into what two classes?

A

Histone Proteins

Non-histone chromosomal proteins (Transcription Factors)

3
Q

How many histone proteins per nucleosome core particle?

A

Eight

4
Q

_____ is protein in which DNA is wound.

What are the protein and DNA together referred to as?

A

Histone octamer

Protein + DNA = Chromatin

5
Q

The lightly packed form of chromatin, highly enriched in genes and often under active transcription.

What percentage of the human genome is this type?

A

Chromatin

92%

6
Q

What is very condensed chromatin, containing very few active genes?

Where is this found?

A

Heterochromatin (thought to be late replicating and genetically inactive)

Found at the centromeres and telemeres

7
Q

What is the position effect?

A

Activity a gene depends on relative position on chromosome

Actively expressed genes will be silenced if relocated near heterochromatin

8
Q

Why are mice great genetic models? What accounts for their differences?

A

90% amount of mouse genome is the same

99% of mouse genes have human analogues

Major proteomic differences

A lot of alternative splicing

9
Q

What percentage of the genome is exons?

A

1.5%

10
Q

What is comparative genome hybridization?

A

Detection of Copy Number Variations (1000 differences)

CGH is done through probing Human Genome CHIP with DNA from one person and comparing it to normal reference.

Being used clinically now and can detect copy number variation.

11
Q

What are long terminal repeats and how do Virus’s utilize them?

A

Identical sequences of DNA 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

12
Q

How are ~100,000 proteins encoded by only 26,000 genes

A

Alternative splicing

15% of mutations affect this

13
Q

What do 99% of introns begin and end with?

A

…GT…….AG…

14
Q

How are histones activated?

How are they deactivated?

A

Acetylation - Histone Acetyl Transferases (HATS)

Deacetylation - Histone Deacetylase (HDAC)

15
Q

How do HDACs and HATs directly regulate gene expression?

A

A ligand binds to a receptor and recruits a coactivator (HATs) after displacing a corepressor (HDACs).

This upregulates transcription factor associated proteins that acetylate the DNA

16
Q

What on histones stands out for Post Translational Modification

A

Histone protein tails

17
Q

How does DNA Methylation occur and on what DNA bases?

A

Methyl groups added to cytosine and adenine by methyltransferase enzymes

Represses Gene when at gene promoter.

18
Q

What does DNA topoisomerase do?

A

Reversible enzyme
Breaks a phosphodiester bond
Changes superhelicity
Relieves supercoiling

19
Q

Why are gene promoter CpG islands considered in carcinogenesis?

A

Acquire abnormal hypermethylation

Transcriptional silencing

Can be inherited by daughter cells following cell division

20
Q

Methylation resulting in chromosomal instability and loss of imprinting.

A

Hypomethylation

21
Q

What happens with Hypermethylation?

A

Associated with gene promoters

Can arise secondary to an oncogene suppressor promotor resulting in its suppression

Can be a epigenetic target for therapy

22
Q

DNA polymerase requires ______ to begin processing.

A

a primer with a free 3’ -OH

23
Q

What is DNA Helicase do?

A

Binds and hydrolyzes ATP

Pries apart DNA at 1000bp/sec

24
Q

What do SSBP do?

A

Helps stabilize the unwound DNA

Prevents the formation of hairpins

25
Q

What are the type one topoisomerase inhibitors and what do they do?

A

Inhibit topoisomerase I during the S phase

Irinotecan/Folfori- used in colorectal cancer

26
Q

Type II Inhibitors of topoisomerase do what?

A

Etoposide, anthracyclines, doxorubicin, and daunorubocin

Etoposide causes secondary leukemias (dose dependent)

Anthracyclines cause cardiotoxicity (dose dependent)

27
Q

What is a pyrimidine dimer and how is it formed?

A

UV radiation, produces covalent linkage between two adjacent pyrimidines (T-T or C-T)

28
Q

What kind of damage can Ionization radiation cause?

A

Double-stranded breaks

29
Q

What is Depuration and how often does it occur?

A

5000 purines lost per day

A purine is lost to an OH group.

Can lead to base deletion

30
Q

What is deamination and how often does it occur?

A

A change from C to U, 100 Bases a day

Can lead to point mutations

31
Q

Methylation of CpG Islands does what

A

Stably silences genes “some are related to cancer” and produces a T mismatched with a G

32
Q

What removes the mismatched pairs due to CpG methylation?

A

A special glycosylase recognizes and removes the T

DNA repair is relatively ineffective in this case however

33
Q

What percentage of C nucleotides are mutated?

How many point mutations does this account for?

A

3%

1/3 of all point mutations

34
Q

Why are well-done meats dangerous?

A

Benzo(a)pyrene a procarcinogen and become BPDE (Carcinogen)

35
Q

What crosslinking agents can cause DNA Damage

A

Nitrogen mustard

Cisplatin

Miomycin C

Carmustin

“NCMC”

36
Q

What are the alkylating agents that can cause DNA damage?

A

Dimethyl sulfate

Methyl methanesulfonate

37
Q

What Intercalating agents can cause cancer?

A

Thalidomide

38
Q

Photoreactivation of thymine dimer

A

Photolyase corrects this with light

39
Q

First step of Base Exclusion repair

A

The altered base is detected by DNA glycosylases

DNA glycosylase removes the base (hydrolyzes N-glycosidic bond)

40
Q

Second Step of Base Exclusion repair

A

AP Endonuclease cuts phosphodiester bond

AP lyase removes deoxyribose phosphate

41
Q

Third step of Nucleotide excision repair

A

DNA polymerase replaces the existing nucleotide

DNA ligase seals nick

42
Q

NER complex does what

A

Is involved in Nucleotide excision repair (NER). Removes DNA segment, polymerase/ligase reform.

43
Q

Faulty NER can cause what?

A

Xanderma pigmentosum, cockayne syndrome

44
Q

What is MER?

A

Mismatch excision repair

The mismatch is recognized and daughter strand is cut out to remove it.

MutS and MutL excise DNA.

45
Q

How are new strands distinguished in MER?

A

E.Coli uses methylation to distinguish strand

Eukaryotes use Okazaki fragments

46
Q

Autosomal dominant mutation in MER causes this disease.

A

Hereditary nonpolyposis colorectal cancer.

47
Q

Nonhomologous vs homologous recombination

A

Nonhomologous leads to end joining.

Homologous leads to using the sister chromatid as a template.

48
Q

A drug that binds to the B subunit of RNA polymerase in bacterial cells

A

Rifampicin

49
Q

What are the checkpoints that ensure the completion of one stage in the cell cycle before the next begins

A

Damage Delays

  1. G1 into S phase blocked
  2. Slows progression in S
  3. Blocks transition from G2 to M phase
50
Q

What disease is characterized by a defective ATM protein, a protein kinase activated by double-strand breaks?

A

Ataxia telangiectasia

Leukemia, lymphoma, y-ray sensitivity

51
Q

Defect in BRCA2 causes what?

A

Repair by homologous recombination compromised

Breast, ovaria, and prostate cancer

52
Q

Caused by Defect in DNA interstrand cross-repair

A

Fanconi anemia froups A-G

53
Q

Post-transcriptional mods can compete for action on _______

A

Lysine

54
Q

A mechanism for regulating gene activity independent of DNA sequence that determines which genes are turned on or off.

What influences it?

A

Epigenetics

55
Q

Precurser SUMO is turned into Mature SUMO how?

A

Sentrin proteases chop an XX domain on the enzyme, leaving a GG tail.