(2): Genomic Regulation Flashcards
1
Q
Mitotic chromosomes are condensed ____ times when compared to interphase chromosomes
A
500
2
Q
Why are chromosomes condensed?
A
To prevent physical damage to DNA
3
Q
142 hydrogen bonds are formed b/w DNA and the ______ in each nucleosome
A
histone octomer
4
Q
Histone proteins are:
A
highly conserved across species
5
Q
Approximately 20% of histone protein aa are either _____ or _____
A
Lysine (Lys) or Arginine (Arg)
6
Q
What are the two classes of proteins that bind to DNA?
A
- Histone proteins
2. Non-histone chromosomal proteins (TFs)
7
Q
Each nucleosome core particle consists of ____ histone proteins
A
8
8
Q
______ + _______ = chromatin
A
Protein + DNA
9
Q
What are “Puffs” in DNA?
A
Sites of active trancsription
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
11
Q
What is heterochromatin?
A
-CONDENSED
- Not active
- Few active genes
12
Q
What info is found on chromosomes?
A
- Genes
- Interspersed DNA that does not contain genes
13
Q
How many bonds b/w G and C?
A
3
14
Q
How many bonds b/w A and T?
A
2
15
Q
Approximately how many genes?
A
25,000
16
Q
Percentage of DNA sequences in exons?
A
ONLY 1.5%
17
Q
microRNA (miRNA), what do they do?
A
- induce degradation of mRNA
- blockage of translation
18
Q
*******Alternative RNA splicing:
What is at the border at the front and end of the intron?
A
GT————-AG
19
Q
Histone Deacetylase (HDAC)?
A
- Removes acetyl groups
- Turns gene OFF
20
Q
Histone Acetylation?
A
- Actively PROMOTES gene expression
- Adds acetyl group
21
Q
Histone Acetylation (HATs)?
A
- Actively PROMOTES gene expression
- Adds acetyl group
22
Q
Transcription factor associated proteins are responsible for:
A
gene activation and repression
23
Q
Histone Post-Translational Modification (PTM)
What are the 5 types?
A
- Methylation
- Ubiquitination
- Acetylation
- Phosphorylation
- Citrullination
24
Q
DNA Methylation
What enzyme does this?
A
Methyl transferase enzymes
25
What does DNA Methylation contribute to?
- Genomic imprinting
- X-chromosome inactivation
- Repression of transposable elements
- Aging
- Carcinogenesis
26
Hyper- and hypo- DNA Methylation in Cancer
Gene promotor CpG Islands:
What happens?
- Transcriptional silencing
| - Can be inherited by daughter cells following cell division
27
DNA polymerase requires ___________ to begin processing
a primer with a free 3'-OH
28
DNA Replication is semi discontinuous: explain
Continuous synthesis on leading strand
Discontinuous synthesis on lagging strand
29
DNA can only synthesize DNA in the ___' to ___' direction
5' to 3'
30
What does TOPOISOMERASE do?
Relieves overwound supercoils (called DNA gyrase in bacteria)
31
Pharmaceutical drugs that target ______________ are used as anti-cancer agents
DNA Topoisomerase
32
DNA damage can occur from UV radiation, which causes??
A covalent TT or CT pyrimidine dimer
33
Ionization radiation causes...
Strand breaks
Chemical modifications of bases
DNA protein cross links broken
34
ADD NON IONIZING RADIATION
SLIDE 64
35
ADD SPONTANEOUS DNA DAMAGE
SLIDE 65
36
ADD DEPURINATION OF A AND G
SLIDE 66
37
SPONTANEOUS
68
38
Benzo(a)pyrene is converted to
BPDE (an epoxide/carcinogen)
Found in well done meat
*Converts from a pro-carcinogen to carcinogen
39
What is an intercalating agent?
Thalidomide
40
What is an alkylating agents?
```
Dimethyl sulfate (DMS)
Methyl methanesulfonate (MMS)
```
41
What are examples of cross-linking agents?
- Nitrogen mustard
- Cisplatin
- Mitomycin C
- Carmustine
42
142 hydrogen bonds are formed b/w DNA and the __________ in each nucleosome
Histone octamer
43
Explain why Histone proteins have some many +++++ charges:
Attracted to NEGATIVELY charged DNA backbone
44
Lysine residues in histone proteins are the target of...
Post translational modifications (PTMs)
45
Each nucleosome core particle consists of a complex of _____ histone proteins
8
46
Who ACTUALLY discovered the structure of DNA?
Rosalind Franklin
47
Human genome consists of ____ chromosomes
46
48
Surprises with human genome:
_____ % of DNA sequence is in exons
1.5%
49
What is a CGH array?
"Comparative genome hybridization" arrary
50
What do CGH arrarys compare?
Copy number variations in human genome
51
What do HDAC's do?
Histone Deacetylase;
Remove acetyl groups from histones
52
What do HATs do?
Histone Acetyl Transferase;
Add acetyl groups to histones
53
When HDAC's remove acetyl groups, what does this do to gene expression?
REPRESSES gene expression
54
When HAT's add acetyl groups to histones, what does this do to gene expression?
PROMOTES gene expression
55
Histone tails are the target of multiple _____
PTMs
56
DNA Methylation
What key processes is this associated with?
- Genomic imprinting
- X-chromosome inactivation
- Repression of transposable elements
- Aging
- Carcinogenesis
57
DNA Methylation
What happens when DNA is methylated at a gene promoter?
Represses gene transcription
58
DNA Methylation
At what sites does DNA get methylated?
Cytosine and Adenine;
59
Alterations of DNA Methylation are important component of ______
Cancer development
60
Gene promoter CpG islands:
Important aspects?
- Aquire abnormal hypermethylation
- Transcriptional SILENCING
- Can be inherited by daughter cells following cell division
61
Hypomethylation of DNA is associated with:
- Chromosomal instability
| - Loss of imprinting
62
Hypermethylation of DNA is associated with:
- Associated with gene promoters
- Secondary gene silencing
- Might be a target for epigenetic therapy
63
DNA polymerase requires a primer with a ___________ to begin processing
free 3' -OH
64
DNA Helicase requires ____ to unwind DNA
ATP
65
Function of TOPOISOMERASE
Relieves overwound supercoils
| called DNA gyrase in bacteria
66
Pharmaceutical drugs that target DNA topoisomerase are used as __________ drugs
Anti-cancer
67
Example of a TOPOISOMERASE inhibitor?
- Irinotecan
- Etoposisde
- Anthracyclines
***Act by blocking the cell cycle, generate single and double stranded breaks, harms integrity of genome
68
UV radiation causes:
Pyrimidine dimers
TT; CT
69
Ionizing radiation causes:
DNA-protein cross links (*thymine-tyrosine crosslink)
70
What are the two examples of spontaneous DNA damage?
- Depurinination
| - Deamination
71
***METHYLATED CYTOSINE RESIDUES in CpG sites/islands are problematic!!!
Why?
-Stably silences genes (Cancer/DNA repair genes)
72
Metabolism can produce Carcinogens! What's an example?
Pro-carcinogen --> BPDE (carcinogen)
In well done grilled meats!
73
What are examples of chemical agents that are cross linking agents?
- Nitrogen mustard
- Cisplatin
- Mitomycin C
- Carmustine
74
What are examples of chemical agents that are alkylating agents?
- Dimethyl sulfate (DMS)
| - Methyl methanesulfonate (MMS)
75
What is an example of an intercalating agent?
-Thalidomide
76
What does direct repair fix?
- Pyrimidine dimers
| - O6 methyl guaninine
77
What does base excision repair fix?
Fix one incorrect nucleotide, detected via DNA GLYCOSYLASE or DNA POL during replication (takes a step back during replication to recruit glycosylase)
78
What does nucleotide excision repair fix?
-Fixes steric hinderance by removing chunks of distorted DNA
79
What does mismatch repair fix?
One incorrect nucleotide in the Daughter strand during replication
80
What are the two types of double strand break repair?
1. Non homologous end joining
| 2. Homologous recombination
81
What occurs during NON HOMOLOGOUS END JOINING?
- Cut out damage, glue together
| * BAD!
82
What occurs during HOMOLOGOUS RECOMBINATION?
Utilize sister chromatid
*Fewer side affects from!! "healthier"
83
What causes Ionizing radiation?
NUKES!!!
Induces large breaks in double strands
84
What causes non-ionizing radiation?
UV RAYS
Pyrimidine dimers
85
What is spontaneous damage?
- Deamination
| - Depurination
86
What happens with Transcription coupled repair?
RNA Pol Stalls,
BER or NER fixes
87
CLINICAL CORRELATION:
Xeroderma Pigmentosum
- Spots on skin
- Caused by non-ionizing radiation
- Pryimidine dimers
***Failure in NTER
88
CLINICAL CORRELATION:
Hereditary Non-Polyposis Colorectal Cancer
***Failure in MER
89
CLINICAL CORRELATION:
Cockayne Disease
- Look old
- Gene ERC6/8 is defective
***Failure in TRANSCRIPTION COUPLED REPAIR
90
CLINICAL CORRELATION:
BRCA
-Tumor suppressor gene
***Failure in HOMOLOGOUS RECOMBINATION
91
What does SUMOylation do?
SUMOylation facilitates ubiquitination which leads to destruction
