Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

MCM Final > Function And Dysfunction In Genomic Regulation > Flashcards

Function And Dysfunction In Genomic Regulation Flashcards

1
Q

What is the total volume of the cell that the nucleus takes up?

A

6%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the very basic explanation of the central dogma?

A

DNA is transcribed to RNA which is translated into proteins.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What enzyme do RNA viruses such as HIV use to incorporate their RNA into host DNA?

A

Reverse transcriptase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Describe the structure of DNA

A

DNA is double stranded and anti parallel, forming a double helix with a major groove and a minor groove.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

The two sides of DNA are held together by what type of interaction?

A

Hydrogen bonds.

A double bonds to T

C triple bonds to G—this is a stronger bond.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Why are mitotic chromosomes condensed 500 times when compared to chromosomes in interphase?

A

This condensation prevents physical damage to the DNA while the chromosomes are separating.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

To condense DNA, it is wrapped around what type of proteins, and how many hydrogen bonds are formed?

What is this DNA-protein structure called?

A

DNA wraps around histone octamers, forming 142 hydrogen bonds.

This structure is referred to as a nucleosome.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What amino acid residues are abundant in histone proteins?

A

Lysine (K) and Arginine (R)

Remember that the location sequence for proteins destined for the nucleus are also rich in K and R. This makes sense because histones need to be transported to the nucleus to make nucleosomes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What residues in the histone are targets of post translational modifications?

A

Lysine is the most highly targeted residue.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the term for NON-HISTONE chromosomal proteins?

A

Transcriptions factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

euchromatin vs heterochromatin

A

Euchromatin is loosely packed, allowing the DNA to be more easily reached for transcription and translation. Genes of highly expressed proteins are euchromatin.

Heterochromatin is very condensed and stains darkly. This DNA is genetically inactive and found near centromeres and telomeres.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Describe the Position Effect

A

Activity of a gene depends on the relative position on the chromosome.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Who first published a paper asserting the double helical structure of DNA? Who actually did all the work to obtain this information?

A

Watson and Crick described this model in a paper in 1953.

Rosiland Franklin produced the images that led to this paper.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Who determined the genetic code, when?

A

Nuremberg, Khorana, and Holley in 1966.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

The Human Genome Project, when and what was it?

What surprising but helpful information was discovered?

A

Started in the 90’s and ended in 2004.

A project to sequence the entire human genome.

Genes in human and mice are INCREDIBLY similar, therefore they are excellent lab models.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

The majority of DNA is…..

A

Non coding/regulatory.

Only 1.5% is coding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What kind of testing can be done to help with personalized medicine?

A

CGH (Comparative Genome Hybridization) arrays.

Compare patient’s DNA against a reference DNA to determine Copy Number Variations (CNV)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

RNAi is carried out by what molecule and how does it work?

A

miRNA—
MicroRNA folds back on itself (double stranded) via hydrogen bonds, and then is cleaved into small pieces via Dicer enzyme. These, now single stranded pieces are carried to target mRNA via protein complex. Once bound to the target mRNA, expression prevented by degrading the target, or by blocking transcription.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

On average, how many alternative splicing products does a gene have?

A

Two.

There are only 26k genes that encode for ~100k proteins.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What base pairs do introns begin and end with?

A

[…GT] and [AG…]

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What do Histone Deacetylase (HDAC) and Histone Acetyl Transferase (HAT) do and how does that relate to gene expression?

A

HDAC—takes acetyl off histone proteins. This allows the DNA to be more condensed, and therefor turning genes off.

HAT—puts acetyl on the histones. This makes the DNA less condensed and more easily accessible, turning the gene on.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What part of the nucleosome undergoes post translational modification most regularly?

What kind of modifications can occur?

A

Histone tails are the target of numerous PTMs.

They can be modified in many ways:

  • Methylation
  • Acetylation
  • Phosphorylation
  • Ubiquitination
  • SUMOylation
  • Citrullination
  • ADP-ribosylation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

DNA Methylation: what kind of enzyme preforms this action, and what does it do to DNA?

A

Methyl transferases add methyl groups to cytosine and adenine.

Methylation represses transcription when at a gene promoter.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What happens when CpG islands are hypermethylated?

A

Gene promoter CpG islands can be hypermethylated. This trascriptionally silences the gene.
This methylation can be inherited by daughter cells. (Epigenetics)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

In what direction does DNA-dependent DNA polymerase synthesize new DNA?

A

DNA is made from 5’-3’

DNA that is being read, is read 3’-5’

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Can DNA polymerase bind directly to DNA and begin synthesizing?

A

No, DNA polymerase requires a primer with a free 3’ -OH to begin

27
Q

Describe the leading strand vs. the lagging strand.

A

Leading strand—synthesized continuously. No prob

Lagging strand—because DNA is synthesized 5’-3’ the lagging strand must synthesize DNA in fragments called Okazaki fragments that are then fused together by DNA-ligase.

28
Q

DNA Helicase

  1. What is its structure?
  2. What does it do?
A
  1. Enzyme with 6 identical subunits that uses ATP
  2. DNA helicase opens up the replication fork and unwinds the DNA. One strand goes through the center hole of the enzyme.
29
Q

What is the function of the Single-Stranded DNA Binding Protein (SSBP)?

A

Binds to exposed single stranded DNA, and prevents the formation of hairpins.

30
Q

DNA Topoisomerase

  1. Function
  2. Target for? Include examples
A
  1. Breaks one phosphodiester bond to relieve super coiling as DNA helicase unwinds the DNA.
  2. Topoisomerase is the target of some anti-cancer medications. These include IRINOTECAN—used for colorectal cancer and ETOPOSIDE—which causes secondary leukemias.
31
Q

What does UV radiation cause, and what does this mean?

A

UV radiation causes THYMINE DIMERS.

This means that two thymines or a thymine and a cytosine make covalent bonds with each other rather than their base pair. This causes a buckle in the DNA.

32
Q

What is depurination, and how will it affect new DNA strands?

A

A form of spontaneous DNA damage resulting in the loss of the purine from the base pair, leaving just a sugar-phosphate behind.

One new strand will be unaffected, the other will have deleted the missing base pair.

33
Q

Describe deamination, and what is the consequence of this?

A

A form of spontaneous DNA damage in which an amine group is lost from the basepair.

ie:
adenine&raquo_space;> hypoxanthine
guanine&raquo_space;> xanthine
cytosine&raquo_space;> uracil

One strand will be unaffected, whereas the other will have the wrong base pair.

34
Q

Name 4 cross-linking agents

A
  1. Nitrogen mustard
  2. Cisplatin
  3. Mitomycin C
  4. Carmustine
35
Q

Name 2 alkylating agents

A 
Dimethyl sulfate (DMS)
Methyl methanesulfonate (MMS)
36
Q

What is one famous intercalating agent, and what was it originally prescribed for?

A

Thalidomide

This was originally prescribed for anti-anxiety and anti nausea purposes for pregnant women in the 50s.

37
Q

Xeroderma Pigmentosum

  1. Dysfunction
  2. Consequence
A
  1. Defect in various XP proteins in the NER complex
  2. Defective NER is unable to repair cyclobutane thymine dimers. Therefore these individuals are very sensitive to direct sunlight and are prone to developing melanoma and squamous cell carcinoma.
38
Q

Hereditary nonpolyposis colorectal cancer

  1. Dysfunction
  2. Consequence
A
  1. Mutation in one of the alleles of genes in the MER complex.
  2. An acquired mutation in the remaining good copy of the gene would make the MER system non functional and would allow for tumor development.

AUTOSOMAL DOMINANT

39
Q

Cockayne syndrome

  1. Dysfunction
  2. Consequence
  3. Clinical findings
A
  1. Rare autosomal recessive, congenital, mutation of ERCC6 and ERCC8 which code for proteins involved in TCR of DNA.
  2. If DNA is not repaired, cell death may occur
  3. Characterized by developmental delay, neurological delay, photosensitivity, progeria, hearing loss, and eye abnormalities. Death occurs within first 2 decades of life.
40
Q

BCRA associated Breast Cancer

  1. Dysfunction
  2. Consequence
A
  1. Mutations in the BCRA (breast cancer susceptibility gene1)
  2. As these are tumor suppressor genes, mutations increase by fivefold the risk for getting breast cancer.
41
Q

Direct repair (Enzymatic repair)

  1. Type of damage repaired
  2. Enzyme/mechanism involved
  3. Associated disorder (if any)
A
  1. Pyrimidine dimers

2. DNA photolyase

42
Q

Base excision repair (BER)

  1. Type of damage repaired
  2. Enzyme/mechanism involved
  3. Associated disorder (if any)
A
  1. Single base mismatches, non distorting alterations (depurination)
  2. DNA glycolase, AP endonuclease
43
Q

Nucleotide excision repair (NER)

  1. Type of damage repaired
  2. Enzyme/mechanism involved
  3. Associated disorder (if any)
A
  1. Chemical adducts that distort DNA (eg. pyrimidine dimers, BPDE-guanine adducts, cisplatin adducts)
  2. NER protein complex, DNA polymerase, DNA ligand
  3. Xeroderma pigmintosum
44
Q

Mismatched excision repair (MER)

  1. Type of damage repaired
  2. Enzyme/mechanism involved
  3. Associated disorder (if any)
A
  1. Mismatched base in daughter strand
  2. MER complex, helicase/endonuclease, DNA polymerase, DNA ligand
  3. Hereditary nonpolyposis colorectal cancer
45
Q

Genes:

MSH2, 3, 6
MLH 1
PMS2

  1. What does a mutation in this gene cause
  2. What enzyme or process is affected
A
  1. Colon cancer

2. MER

46
Q

Genes:

Xeroderma pigmentosum (XP) groups A-G

  1. What does a mutation in this gene cause
  2. What enzyme or process is affected
A
  1. Skin cancer, UV sensitivity, neurological abnormalities

2. NER

47
Q

Genes:
BRCA2

  1. What does a mutation in this gene cause
  2. What enzyme or process is affected
A
  1. Breast, ovarian, and prostate cancer

2. Repair by homologous recombination

48
Q

Ataxia telangiectasia (AT)

  1. What does a mutation in this gene cause
  2. What enzyme or process is affected
A
  1. Leukemia, lymphoma, genome instability

2. ATM protein—a protein kinase activated by double strand breaks.

49
Q

Franconi anemia groups A-G

  1. What does a mutation in this gene cause
  2. What enzyme or process is affected
A
  1. Congenital abnormalities, leukemia, genome instability

2. DNA interstrand cross-link repair.

50
Q

Describe base excision repair (BER)

A

For single base mismatches and non distorting alterations.

  1. Altered base is detected by DNA glycosylase
  2. DNA glycosylase removes base (hydorlyzes n-glycosidic bond)
  3. AP endonuclease cuts phosphodiester bond
  4. AP lyase removes deoxyribose phosphate
  5. DNA polymerase beta replaces excised nucleotide
  6. DNA ligase seals nick
51
Q

Describe nucleotide excision repair (NER)

A

For repair of chemical adducts that distort the DNA

  1. NER complex recognizes distortion and nicks DNA on both sides of the damaged site.
  2. Remove stretch of DNA with damage
  3. DNA polymerase fills in the gap
  4. DNA ligase seals up the nick

DISEASES: xeroderma pigmentosum, cockayne syndrome

52
Q

Mismatch excision repair (MER)

A

For incorrect base in newly synthesized daughter strand

  1. MER complex binds to DNA and recognizes mismatch
  2. Daughter strand is cut, and segment with mismatch is removed
  3. DNA polymerase ? Fills gap
  4. DNA ligase seals the nick

DISEASE: HNPCC (hereditary nonpolyposis colorectal cancer)

53
Q

There are two ways to repair a double stranded break, what are they and how are they different?

A
  1. Nonhomologous end joining— there is a loss of DNA sequence due to degradation from the ends.
  2. Homologous recombination—using sister chromatids, the damage is repaired accurately with no loss of information.
54
Q

What are some causes of double stranded DNA breaks?

A

Ionizing radiation, replication error, and oxidizing agents. If they are not fixed, chromosomes would fall apart.

55
Q

Transcription-coupled repair (TCR)

A

Cells can direct DNA repair to sequences that are actively being transcribed via linking RNA polymerase with DNA repair. Sequences urgently need repair.

RNA polymerase stalls at lesions, and directs repair to the cite.

TCR works with BER, NER, etc to repair DNA as damage occurs.

56
Q

TCR in Cockayne syndrome, specifically.

A

There is a defect in TCR that leads to RNA polymerase being permanently stalled at sites of damage in important genes.

Leads to growth retardation, skeletal abnormalities, and photosensitivity.

57
Q

What diseases can be treated with inhibitors of HAT?

A

Cancer, Alzheimer’s, RA

58
Q

What HDAC inhibitor drugs are used for to treat cancer?

A

Valproic acid, vorinostat (also used as anticonvulsives)

59
Q

Cancer cells are very sensitive to inhibitors of what specific kind of HDAC?

A

Histone core lysine deacetylases.

60
Q

What is a side affect of rifampicin

A

Upregulation of hepatic cytochrome P-450 enzymes which increase the metabolism of other drugs.

61
Q
  1. True or False: different types of PTM can target the same lysine residue?
  2. PTM of lysine residues can be affected by PTM of adjacent/different residues?
A

1 & 2: TRUE

62
Q

Five things that contribute to Epigenetics

A
  1. Development (in utero or childhood)
  2. Environmental chemicals
  3. Drugs
  4. Aging
  5. Diet
63
Q

Hypermethylation of CpG islands leads to what?

A

Stable silencing

64
Q

What is ubiquitin, and how does it work?

A

Ubiquitin is a small protein that is present in all eukaryotic cells.

Ubiquitin is a tag of sorts, being stuck to other proteins via lysine residues.

Ubiquitin can be used in many ways, indicating different fates of the protein:

  1. Monoubiquitination
  2. Multi-monoubiquitination
  3. Mixed heterogeneous polyubiquitination
  4. Homogenous polyubiquitination

MCM Final (12 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions