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Block 5 Cell Structure & Function > Mutagenesis and Recombination > Flashcards

Mutagenesis and Recombination Flashcards

1
Q

What is the oxidation of bases?

What kind of mutagenesis is it?

A

Oxidation of base interrupts the DNA strand.

Endogenous mutagenesis.

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2
Q

What is alkylation of bases? Common example?

Type of mutagenesis?

A

An alkyl group adds to a base, usually a methyl group, causes CROSS LINKAGES.
Endogenous mutagenesis

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3
Q

What is the hydrolysis of bases? Types?

Type of mutagenesis?

A
  1. Hydrolysis occurs with base, resulting in loss of amine group (deamination) , loss of purine (depurination) or loss of pyrimidine (depyrimidination).
  2. Endogenous mutagenesis
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4
Q

Bulky adduct formation is what type of mutagenesis?

A

Endogenous

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5
Q

Mismatch of bases is what type of mutagenesis?

A

Endogenous

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6
Q

Most common deaminations? What happens? Likelihood of repair?

A

Cytosine deaminated to Uracil. Likely identified and repaired.
Methyl C deaminated to T. no repair since it looks normal.

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7
Q

What are the less common deaminations? What happens? Likelihood of repair?

A

Adenine deaminated to hypoxanthine (Hx). This could base pair with C, but since it isn’t a DNA base it will most likely be repaired.
G can be deaminated (Not explained in lecture)

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8
Q

Why are nitrates and nitrites bad? Possible shield from the effects is what?

A

They can form nitrous acid, which in the presence of stomach acid can be converted to nitrosamines. Nitrosamines are carcinogens that cause deaminations.
Vitamin C can help stop this from occurring.

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9
Q
  1. UV-B light is what kind of mutagenesis?
  2. What happens?
  3. Repair?
A
  1. Exogenous mutagenesis
  2. DIRECTLY damages DNA by forming cross link b/w pyrimidine bases. (T-T, C-C, or T-C dimers)
  3. Difficult to repair, and can cause melanomas.
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10
Q
  1. UV-A light is what kind of mutagenesis?

2. What happens?

A
  1. Exogenous mutagenesis.

2. INDIRECTLY damages DNA by causing the formation of free radicals, which can then go and damage DNA.

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11
Q
  1. Ionizing radiation is what kind of mutagenesis?

2. What happens?

A
  1. Exogenous mutagenesis.

2. Causes formation of hydroxyl radical group, that can lead to single and double stranded breaks in DNA

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12
Q

Elevated temperature causes what kind of mutagenesis?

What happens?

A

Exogenous mutagenesis. Increases rate of depurination and single stranded breaks.

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13
Q

Industrial chemicals and pollution are what kind of mutagenesis?

A

Exogenous mutagenesis.

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14
Q
  1. Intercalating agents are what type of mutagen?
  2. What happens?
  3. Common examples?
A
  1. Exogenous
  2. Chemicals slide between stacked bases. Have planar structure to mimic base. Cause FRAMESHIFT mutations, and indels. Also prevent transcription/replication.
  3. Benzopyrene- In tobacco smoke and soot
    Aflatoxins–bulky base, Nitrogen mustard– inter/intra strand ligation
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15
Q
  1. Where does Aflatoxin B1 come from?
  2. What does it do?
  3. Defense against it?
A
  1. Fungal mold on corn, peanuts, peanut butter
  2. If activated, it becomes a compound that acts as a DNA adduct or intercalating agent.
  3. Liver should be able to stop this from ever activating, but can mess up.
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16
Q

Human papilloma virus can cause?

Hepatitis B can cause?

A
  1. Cervical cancer

2. Liver cancer

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17
Q

Epstein-Barr virus can cause (mutagen)

Helicobacter pylori can cause?

A
  1. Lymphoma

2. Gastric cancer

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18
Q

Which cancer is the #1 killer?

A

Lung cancer

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19
Q

Radiation therapy causes what?

A

Double stranded breaks leading to apoptosis, and massive amounts of ROS production which leads to apoptosis.

20
Q

Bleomycin can cause?

A

DS breaks

21
Q

Psoralen derivatives and mitomycin C cause?

A

Interstrand cross-links.

22
Q

What is a transition?

A

pyrimidine to pyrimidine, or purine to purine

23
Q

What is a transversion?

A

pyrimidine to purine, or visa versa.

24
Q

Type of mutation in sickle cell anemia?

What happens in the mutation?

A

Substitution of GAG to GTG.

Glu-Val in beta-globin

25
Q

When does/can homologous recombination occur?

Why is it done?

A

During meiosis, but DNA strands have to be extended and ALMOST IDENTICAL! They have to be very similar.
Introduces genetic variation, but also used as a type of DNA repair.

26
Q

What are the steps of homologous recombination? (Don’t include resolution)

A
  1. Begins with programed DS break in one of the homologs.
  2. RecA/Rad51 protein binds to ONE strand of DNA (SSBP), and then pairs it with the homologous region on a different DOUBLE STRANDED DNA
  3. Triple strand is formed with help of RecA. RecA and ATP allow the invading strand to displace some of a strand, forming a new section of DS DNA
  4. DNA synthesis extends invading strand and ligation occur to fill in missing parts, forming a Double Holliday Structure
27
Q

Explain Double Holliday Junction resolution with crossover

*swap large or small regions of chromosomes?

A

homologous recombination proceeds it.
With crossover:
1. A vertical cut is made in each outside, non involved strand, as well as horizontally on the “x” (further x from it)
2. The short outside pieces made by the vertical cuts switch places, and the horizontal cut pieces join to their “continuous” strand, which is in front of them.
3. This results in FOUR newly combined strands.
**swap large regions of chromosomes

28
Q

Explain double holliday junction resolution without crossover

A

Without crossover:

  1. Horizontal cuts are made at each x
  2. Horizontal cut pieces join with what is continuous/in front of them, forming TWO newly combined strands (One in each homologue), one complete original (outside strand of homologue that didn’t have the DS break at the start), and the outside chromosome on the other side is also original (however, polymerase used a homologue to copy a piece).
29
Q

Different allele ratios than expected might occur in gametes due to what? (even if linkage is present)

A

Gene conversion (heteroduplex thing)

30
Q

Explain DNA mismatch after recombination, and what happens with repair and without repair.
in crossover or no crossover?

A

IN NO CROSSOVER
After recombination, maternal and paternal DNA might have a part that differs, forming a heteroduplex.
With repair: One allele in the mismatch is excised, leaving gap in strand. It is filled in by copying the other strand. This is GENE CONVERSION.

Without repair: The mismatch is essentially ignored, so the replication just happens.

31
Q

What is necessary for site-specific recombination or DNA transposition to occur? 2

A
  1. A specific and short “recombination site” in DNA. However, the DNA strands to not have to be really similar like they do in homologous recombination.
  2. Recombination enzymes (recombinases)
32
Q

Which type of recombination can change gene order?

A

Site-specific recombination and DNA transposition

33
Q

What does site-specific recombination allow to occur? 3

A
  1. A DNA strand can be integrated into another
  2. A DNA piece could be removed from a strand
  3. A piece of a DNA strand could be inverted.
34
Q

How does MRSA relate to site-specific recombination?

A

Horizontal gene transfer and site-specific recombination allows bacteria to transfer resistance to other bacteria.

35
Q

VDJ Recombination: What is this used for, and explain the following players: VDJ recombinase, RAG1, RAG2,
site specific!!!

A

used by IMMATURE LYMPHOCYTES to acquire genes specific to an antigen. (antibody and t cell diversity)
RAG1 and 2 are genes coding for VDJ recombinases which recognize the recombination signal sequence.

36
Q

Classes of transposons:
What do “DNA Transposons” do? Enzyme required?
Example?

A

Simplest class. Mobile DNA segment relocates using transposase enzyme. autonomous, transposase.
Example: P element

37
Q

Classes of transposons:
What do “Retroviral Retrotransposons” do? Enzyme required?
Example?

A

RNA sequences transcribed into DNA, and then insert into DNA.
Enzymes: Reverse transcriptase and integrase
Example: HIV

38
Q

Classes of Transposons:
What do “Non-retroviral Retrotransposons” do? Enzyme required?
Example?
Prevalent in what organisms?

A

Enzymes: Reverse Transcriptase (from other sources) and endonuclease
Examples: LINE L-1, and SINE Alu elements.
Prevalent in humans in ancient times, though no longer happens. — MAJOR part of genome.

39
Q

What percentage of our genome is non-coding? What percentage of non-coding is repeats?

A

98%. 50% of that is repeats (much of which is LINEs and SINEs)

40
Q

Are LINES and SINES coding or non-coding? How can they affect our DNA?

A

The are non-coding, and so can only affect DNA if they move to a coding region.

41
Q

example of disease LINE L1 can cause? How?

A

Hemophilia. L1 inserts into gene that codes for a clotting factor, and so it can no longer be transcribed.
*L1 line element, gene for factor VIII

42
Q

DNA transposition can have what effects on DNA?

A

Can make genes more active, less active, or no effect. Depends on what/where.

43
Q

What are the 3 types of chemotherapy? What are the drugs of each class? What is the idea in mechanism for each class?

A
  1. Alkylating agents and platinum-based drugs: cyclophosphamide, cisplatin, carboplatin
    - Cross-link DNA and form DNA adducts
  2. Anti-metabolites: methotrexate, 5-flourouracil (5-FU)
    - Inhibit DNA synthesis
  3. Organic drugs and natural products: doxorubicin, andriamycin, taxol, paclitaxel, vincristine, vinblastine
    - Either stabilize or inhibit MT assembly by binding to tubulin, or inhibit topo 2
44
Q

Who has transposons? What sequences of DNA can they jump in to?

A

Eukaryotes. Can jump into ANY sequence of DNA.

45
Q

what two things make spontaneous (endogenous) errors?

A

ROS, replicatoin errors

46
Q

what resolves junctions in holliday junctions?

A

endonuclease

Block 5 Cell Structure & Function (7 decks)

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