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MCM Exam 2 > (2): Genomic Regulation > Flashcards

(2): Genomic Regulation Flashcards

1
Q

Mitotic chromosomes are condensed ____ times when compared to interphase chromosomes

A

500

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2
Q

Why are chromosomes condensed?

A

To prevent physical damage to DNA

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3
Q

142 hydrogen bonds are formed b/w DNA and the ______ in each nucleosome

A

histone octomer

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4
Q

Histone proteins are:

A

highly conserved across species

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5
Q

Approximately 20% of histone protein aa are either _____ or _____

A

Lysine (Lys) or Arginine (Arg)

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6
Q

What are the two classes of proteins that bind to DNA?

A
  1. Histone proteins

2. Non-histone chromosomal proteins (TFs)

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7
Q

Each nucleosome core particle consists of ____ histone proteins

A

8

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8
Q

______ + _______ = chromatin

A

Protein + DNA

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9
Q

What are “Puffs” in DNA?

A

Sites of active trancsription

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10
Q

What is Euchromatin?

A

-LIGHTLY packed

  • Highly riches in genes
  • Usually under active transcription
  • Most active portion of the genome
  • Approx 92 percent of human genome is euchromatic
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11
Q

What is heterochromatin?

A

-CONDENSED

  • Not active
  • Few active genes
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12
Q

What info is found on chromosomes?

A
  • Genes

- Interspersed DNA that does not contain genes

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13
Q

How many bonds b/w G and C?

A

3

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14
Q

How many bonds b/w A and T?

A

2

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15
Q

Approximately how many genes?

A

25,000

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16
Q

Percentage of DNA sequences in exons?

A

ONLY 1.5%

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17
Q

microRNA (miRNA), what do they do?

A
  • induce degradation of mRNA

- blockage of translation

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18
Q

*******Alternative RNA splicing:

What is at the border at the front and end of the intron?

A

GT————-AG

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19
Q

Histone Deacetylase (HDAC)?

A
  • Removes acetyl groups

- Turns gene OFF

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20
Q

Histone Acetylation?

A
  • Actively PROMOTES gene expression

- Adds acetyl group

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21
Q

Histone Acetylation (HATs)?

A
  • Actively PROMOTES gene expression

- Adds acetyl group

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22
Q

Transcription factor associated proteins are responsible for:

A

gene activation and repression

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23
Q

Histone Post-Translational Modification (PTM)

What are the 5 types?

A
  • Methylation
  • Ubiquitination
  • Acetylation
  • Phosphorylation
  • Citrullination
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24
Q

DNA Methylation

What enzyme does this?

A

Methyl transferase enzymes

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25
Q

What does DNA Methylation contribute to?

A
  • Genomic imprinting
  • X-chromosome inactivation
  • Repression of transposable elements
  • Aging
  • Carcinogenesis
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26
Q

Hyper- and hypo- DNA Methylation in Cancer

Gene promotor CpG Islands:

What happens?

A
  • Transcriptional silencing

- Can be inherited by daughter cells following cell division

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27
Q

DNA polymerase requires ___________ to begin processing

A

a primer with a free 3’-OH

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28
Q

DNA Replication is semi discontinuous: explain

A

Continuous synthesis on leading strand

Discontinuous synthesis on lagging strand

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29
Q

DNA can only synthesize DNA in the ___’ to ___’ direction

A

5’ to 3’

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30
Q

What does TOPOISOMERASE do?

A

Relieves overwound supercoils (called DNA gyrase in bacteria)

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31
Q

Pharmaceutical drugs that target ______________ are used as anti-cancer agents

A

DNA Topoisomerase

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32
Q

DNA damage can occur from UV radiation, which causes??

A

A covalent TT or CT pyrimidine dimer

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33
Q

Ionization radiation causes…

A

Strand breaks
Chemical modifications of bases
DNA protein cross links broken

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34
Q

ADD NON IONIZING RADIATION

A

SLIDE 64

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35
Q

ADD SPONTANEOUS DNA DAMAGE

A

SLIDE 65

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36
Q

ADD DEPURINATION OF A AND G

A

SLIDE 66

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37
Q

SPONTANEOUS

A

68

38
Q

Benzo(a)pyrene is converted to

A

BPDE (an epoxide/carcinogen)

Found in well done meat

*Converts from a pro-carcinogen to carcinogen

39
Q

What is an intercalating agent?

A

Thalidomide

40
Q

What is an alkylating agents?

A 
Dimethyl sulfate (DMS)
Methyl methanesulfonate (MMS)
41
Q

What are examples of cross-linking agents?

A
  • Nitrogen mustard
  • Cisplatin
  • Mitomycin C
  • Carmustine
42
Q

142 hydrogen bonds are formed b/w DNA and the __________ in each nucleosome

A

Histone octamer

43
Q

Explain why Histone proteins have some many +++++ charges:

A

Attracted to NEGATIVELY charged DNA backbone

44
Q

Lysine residues in histone proteins are the target of…

A

Post translational modifications (PTMs)

45
Q

Each nucleosome core particle consists of a complex of _____ histone proteins

A

8

46
Q

Who ACTUALLY discovered the structure of DNA?

A

Rosalind Franklin

47
Q

Human genome consists of ____ chromosomes

A

46

48
Q

Surprises with human genome:

_____ % of DNA sequence is in exons

A

1.5%

49
Q

What is a CGH array?

A

“Comparative genome hybridization” arrary

50
Q

What do CGH arrarys compare?

A

Copy number variations in human genome

51
Q

What do HDAC’s do?

A

Histone Deacetylase;

Remove acetyl groups from histones

52
Q

What do HATs do?

A

Histone Acetyl Transferase;

Add acetyl groups to histones

53
Q

When HDAC’s remove acetyl groups, what does this do to gene expression?

A

REPRESSES gene expression

54
Q

When HAT’s add acetyl groups to histones, what does this do to gene expression?

A

PROMOTES gene expression

55
Q

Histone tails are the target of multiple _____

A

PTMs

56
Q

DNA Methylation

What key processes is this associated with?

A
  • Genomic imprinting
  • X-chromosome inactivation
  • Repression of transposable elements
  • Aging
  • Carcinogenesis
57
Q

DNA Methylation

What happens when DNA is methylated at a gene promoter?

A

Represses gene transcription

58
Q

DNA Methylation

At what sites does DNA get methylated?

A

Cytosine and Adenine;

59
Q

Alterations of DNA Methylation are important component of ______

A

Cancer development

60
Q

Gene promoter CpG islands:

Important aspects?

A
  • Aquire abnormal hypermethylation
  • Transcriptional SILENCING
  • Can be inherited by daughter cells following cell division
61
Q

Hypomethylation of DNA is associated with:

A
  • Chromosomal instability

- Loss of imprinting

62
Q

Hypermethylation of DNA is associated with:

A
  • Associated with gene promoters
  • Secondary gene silencing
  • Might be a target for epigenetic therapy
63
Q

DNA polymerase requires a primer with a ___________ to begin processing

A

free 3’ -OH

64
Q

DNA Helicase requires ____ to unwind DNA

A

ATP

65
Q

Function of TOPOISOMERASE

A

Relieves overwound supercoils

called DNA gyrase in bacteria

66
Q

Pharmaceutical drugs that target DNA topoisomerase are used as __________ drugs

A

Anti-cancer

67
Q

Example of a TOPOISOMERASE inhibitor?

A
  • Irinotecan
  • Etoposisde
  • Anthracyclines

***Act by blocking the cell cycle, generate single and double stranded breaks, harms integrity of genome

68
Q

UV radiation causes:

A

Pyrimidine dimers

TT; CT

69
Q

Ionizing radiation causes:

A

DNA-protein cross links (*thymine-tyrosine crosslink)

70
Q

What are the two examples of spontaneous DNA damage?

A
  • Depurinination

- Deamination

71
Q

***METHYLATED CYTOSINE RESIDUES in CpG sites/islands are problematic!!!

Why?

A

-Stably silences genes (Cancer/DNA repair genes)

72
Q

Metabolism can produce Carcinogens! What’s an example?

A

Pro-carcinogen –> BPDE (carcinogen)

In well done grilled meats!

73
Q

What are examples of chemical agents that are cross linking agents?

A
  • Nitrogen mustard
  • Cisplatin
  • Mitomycin C
  • Carmustine
74
Q

What are examples of chemical agents that are alkylating agents?

A
  • Dimethyl sulfate (DMS)

- Methyl methanesulfonate (MMS)

75
Q

What is an example of an intercalating agent?

A

-Thalidomide

76
Q

What does direct repair fix?

A
  • Pyrimidine dimers

- O6 methyl guaninine

77
Q

What does base excision repair fix?

A

Fix one incorrect nucleotide, detected via DNA GLYCOSYLASE or DNA POL during replication (takes a step back during replication to recruit glycosylase)

78
Q

What does nucleotide excision repair fix?

A

-Fixes steric hinderance by removing chunks of distorted DNA

79
Q

What does mismatch repair fix?

A

One incorrect nucleotide in the Daughter strand during replication

80
Q

What are the two types of double strand break repair?

A
  1. Non homologous end joining

2. Homologous recombination

81
Q

What occurs during NON HOMOLOGOUS END JOINING?

A
  • Cut out damage, glue together

* BAD!

82
Q

What occurs during HOMOLOGOUS RECOMBINATION?

A

Utilize sister chromatid

*Fewer side affects from!! “healthier”

83
Q

What causes Ionizing radiation?

A

NUKES!!!

Induces large breaks in double strands

84
Q

What causes non-ionizing radiation?

A

UV RAYS

Pyrimidine dimers

85
Q

What is spontaneous damage?

A
  • Deamination

- Depurination

86
Q

What happens with Transcription coupled repair?

A

RNA Pol Stalls,

BER or NER fixes

87
Q

CLINICAL CORRELATION:

Xeroderma Pigmentosum

A
  • Spots on skin
  • Caused by non-ionizing radiation
  • Pryimidine dimers

***Failure in NTER

88
Q

CLINICAL CORRELATION:

Hereditary Non-Polyposis Colorectal Cancer

A

***Failure in MER

89
Q

CLINICAL CORRELATION:

Cockayne Disease

A
  • Look old
  • Gene ERC6/8 is defective

***Failure in TRANSCRIPTION COUPLED REPAIR

90
Q

CLINICAL CORRELATION:

BRCA

A

-Tumor suppressor gene

***Failure in HOMOLOGOUS RECOMBINATION

91
Q

What does SUMOylation do?

A

SUMOylation facilitates ubiquitination which leads to destruction

MCM Exam 2 (13 decks)

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