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Chapter 10
Chapter 10 Evans
79
Microbiology
Undergraduate 1
02/28/2011

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Term
abasic site (AP site)
Definition
An AP site (apurinic/ apyrimidinic site) is a location in DNA that has neither a purine nor a pyrimidine base usually due to DNA damage. Can also be formed by spontaneous depurination, but also occur as intermediates in base excision repair.
Term
alkylating agent
Definition
they are classified according to their nucleophilic or eletrophilic character,---nucleophilic deliver the equivalent of an alkyl anion. These compounds typically can add to an electron deficient carbon atom such as at a carbonyl group. --- electrophilic alkylating agents deliver the equivalent of an alkyl cation.
Term
alkylation
Definition
is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical a carbanion or a carbene or their equivalents.
Term
AP endonuclease
Definition
is an enzyme that is involved in the DNA base excision repair pathway. Its main role is the repair of damaged or mismatched nucleotides in DNA is to create a nick in the phosphodiester backbone of the AP site created when DNA glycosylase removes the damaged base.
Term
carcinogen
Definition
is any substance, radionuclide or radiation that is an agent directly involved in causing cancer. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes.
Term
cross-linking
Definition
are bonds that link one polymer chain to another. They can be covalent bonds or ionic bonds.
Term
pyrmidine dimer
Definition
are molecular lesions formed from thymine or cytosine bases in DNA via photochemical reactions. UV light induces the formation of covalent linkages by reactions localized on the C=C double bonds.
Term
dealkylation
Definition
The removal of alkyl groups ?
Term
deamination
Definition
The removal of an amine group from a molecule. In the human body this primarily takes place in the liver.
Term
DNA glycosylase
Definition
are a family of enzymes involved in base excision repair. They catalyze the first step in base excision repair, by removing the damaged nitrogenous base while leaving the sugar phosphate backbone intact, creating the AP site.
Term
DNA glycosylase/lyase
Definition
are a family of enzymes involved in base excision repair. Base excision repair is the mechanism by which damaged bases in DNA are removed and replaced. They catalyze the first step of this process.
Term
double-strand break
Definition
This is when both strands in the double helix are severed.
Term
error-prone DNA polymerase
Definition
in cases where DNA damage has escaped the DNA repair system, this allow the lesions to be bypassed during DNA replication
Term
hydrolytic cleavage
Definition
is a chemical reaction during which molecules of water are split into hydrogen cations, and hydroxide anions, in the process of chemical mechanism. It is used to break down certain polymers.
Term
LexA
Definition
is a repressor enzyme that represses the SOS response genes coding for DNA polymerases required for repairing DNA damage. It is linked to RecA
Term
missense mutation
Definition
is a point mutation in which a single nucleotide is changed, resulting in a codon that codes for different amino acid (mutations that change an amino acid to stop condon are considered nonsense mutations, not missense
Term
mismatch repair
Definition
is a system for recognizing and repairing erroneous insertion, deletion and mis-incorporation of bases that can arise during DNA replication and recombination as well as repairing some forms of DNA damage
Term
mutagen
Definition
is a physical or chemical agent that changes the genetic material, usually DNA of an organism, and thus increases the frequency of mutation above the natural background level.
Term
nonsense mutation
Definition
is a point mutation in a sequence of DNA that results in a premature stop codon, or a nonsense codon in the transcribed mRNA, and in a truncated, incomplete and usually nonfunctional protein product.
Term
nucleotide excision repair
Definition
is a DNA repair mechanism. It removes the vast majority of UV induced DNa damage, mostly in the form of thymine dimers. This recognizes bulky distortions in the shape of the DNA double helix.
Term
photolyase
Definition
Are DNA repair enzymes that repair damage caused by exposure to ultraviolet light.
Term
RecA
Definition
is a protein essential for the repair and maintenance of DNA. In the bacterial SOS response, it functions in the cleavage of the LexA repressor and the lambda repressor. Also holds single and double strands together.
Term
SOS response
Definition
is a global response to DNA damage in which the cell cycle is arrested and DNA repair and mutagenesis are induced.
Term
tautomer
Definition
are isomers of readily interconvert by a chemical reaction. It is common that this reaction results in the formal migration of a hydrogen atom or proton accompanied by a switch of a single bond and adjacent double bond.
Term
transition mutation
Definition
is a point mutation that changes a purine nucleotide to another (A<->G) or a pyrimidine to another (C<->T)
Term
translesion DNA synthesis
Definition
is a DNA damage tolerance process that allows the DNA replication machinery to replicate past DNA lesions such as thymine dimers or AP sites. It involves switching out regular DNA polymerases for specialized translesion polymerases, often with larger active sites that can facilitate the insertion of bases opposite damaged nucleotides.
Term
transversion mutation
Definition
is the substitution of a purine for a pyrimidine. Can be caused by ionizing radiation and alkylating agents.
Term
UvrABC endonuclease
Definition
Is involved in DNA repair by nucleotide excision repair.
1. They form a dimer
2. The UvrA dimer binds with UvrB and forms a trimer that is able to detect DNA damage.
3. The UvrB part ofthe trimer attaches to the damaged site
4. UvrA is released, UvrC binds to it forming UvrBC dimer
5 This is responsible for cleaving the nucleotides
6. DNA helicase II (sometimes called UvrD then comes in an removes it
7 DNA poly I comes in and fills in the correct nucleotide sequence
Term
Xeroderma pigmentosum
Definition
is a autosomal recessive genetic disorder of DNA repair in which the ability to repair damage caused by UV light is deficient.
Term
What are some ways that DNA can be damaged?
Definition
Radiation (UV, gamma, x ray)
hydrolytic cleavage
oxidative damage,
alkylation
cross linking
Term
What are the pathways for DNA repair
Definition
-photoreactivation
-base excision repair
-nucleotide excision repair,
-mismatch repair
Term
What does translesion DNA synthesis do
Definition
It allows damaged regions to be bypassed by error prone DNA synthesis without repairing the damage.
Term
UV light induces damage and causes damage in what?
Definition
B DNA
Term
DNA lesions can lead to what
Definition
Deletions, duplications, inversions, and translocations
Term
_____ of N glycosyl bonds and bonds linking amine groups are significant forms of of DNA damage.
Definition
Hydrolytic cleavage
Term
N glycosyl bond cleavage leads to what
Definition
formation of an abasic or AP site
Term
What does an Ap site do
Definition
Its formation sensitizes the neighboring phosphodiester bond to cleave.
Term
Hydrolytic deamination converts cytosine, guanine, and adenine to ______, ________. and _________ respectively
Definition
Uracil, xanthine, and hypoxanthine
Term
What is the Ames test? What is it useful for?
Definition
It is used to detect mutagens. in this test, the potential mutagenic agent is tested for its ability to cause the reversion of a histidine requiring bacterium back to the His+ phenotype
Term
Alkylating agents are highly reactive electrophiles that transfer what
Definition
methyl ethyl or large alkyl groups to DNA
Term
Pyrimidine dimers can be reversed by what
Definition
photoreactivation
Term
Some alkylation damage can be directly reversed by what?
Definition
dealkylation
Term
What is the main pathway for repair of DNA damage caused by deamination oxidation and alkylation
Definition
Base excision repair
Term
Nucleotide excision repair involves what
Definition
-Damage recognition
-incision in the DNA on both sides of the damage,
-excision of the damaged DNA
-synthesis of a new strand,
-ligation of the nick
Term
Bacterial nucleotide excision repair involves what
Definition
-UvrABC endonuclease,
-UvrD
-DNA polymerase I
-Ligase
Term
What does the DNA mismatch repair system do
Definition
it corrects rare base pair mismatches and short deletions or insertions introduced during DNA replication
Term
What are responsible for recognition of the mismatch and incision of the nearest unmethylated GATC sequence
Definition
MutS, MutL, and MutH
Term
Translesion synthesis does not repair the lesion, but instead does what
Definition
Allows the cell to survive DNA damage that has not been repaired.
Term
The SOS response is what?
Definition
A multigene response to DNA damage in E coli after UV irradiation or a chemically induced chromosomal change.
Term
Humans have at least how many template dependent DNA polymerases. Their main function is what?
Definition
14, DNA repair.
Term
UV induced DNA damage is mainly in the form of what?
Definition
dimer formation between adjacent pyrimidine bases on the same DNA strand
Term
Water mediated deamination converts cytosine to ____
Definition
uracil
Term
Ionizing radiation and cellular respiration both produce ____
Definition
reactive oxygen species
Term
Some nitrogens and oxygens in DNA are targets of alkylating agents because they are
Definition
electron rich
Term
The ames test is based upon the idea that a mutagen will
Definition
revert a percentage of histidine mutants to wild type
Term
Photolyases use light energy to repair___
Definition
pyrimidine dimers
Term
Damage to DNA bases caused by deamination, oxidation and alkylation is mainly repaired by
Definition
nucleotide excision repair
Term
In nucleotide excision repair, damaged DNA is detected by
Definition
recognition of helical disortion
Term
Which of the is required for mismatch repair in E.coli
Definition
helicase activity
SSB protein
DNA ligase
Term
The SOS response signal is
Definition
a nucleoprotein filament composed of single stranded DNA and RecA
Term
What mechanisms would an E. Coli cell use to repair pyrimidine dimers?
Definition
Nucleotide excision repair and photoreactivation
Term
DNA damage is caused by _____ cleavage reactions
Definition
hydrolytic
Term
_____ can be detected based on their ability to restore mutant gene activity.
Definition
Mutagens
Term
T or F- reactive oxygen species damage DNA
Definition
True
Term
How does E. coli mismatch repair machinery know which strand to repair?
Definition
The unmethylated strand is always repaired
Term
____ reverses damage done to DNA caused by pyrimidine dimer formation
Definition
Photolyase
Term
Error prone DNA polymerases catalyze ______ DNA synthesis
Definition
translesion
Term
____ and LexA regulate the E. coli SOS response
Definition
RecA
Term
The ____ repair pathway remove and replaces damaged bases.
Definition
Base excision
Term
The ____ repair pathway removes bulky adduct from DNA by excising an oligonucleotide bearing the lesion and replacing it with new DNA
Definition
nucleotide excision
Term
T or F- Many environmental agents must be modified by cell metabolism before they can alkylate DNA
Definition
True
Term
DNA has three kinds of bonds with the potential for hydrolytic damage, namely: ______, n-glycosyl bonds, and bonds linking amine groups to bases.
Definition
phosphodiester bonds
Term
DNA has electron rich atoms that are readily attacked by electron-seeking chemicals called
Definition
electrophiles
Term
____ is the repair of UV-damaged DNA by a light dependent enzymatic reaction.
Definition
Photoreactivation.
Term
_____ is a genetic disorder of DNA repair in which the ability to repair damage caused by UV light is deficient
Definition
Xeroderma pigmentosum
Term
T or F- There are a variety of DNA repair mechanisms, but all of them depend on the existence of two copies of the genetic information, one in each chromosome of a diploid organism
Definition
False-Repair depends on the two copies of genetic information contained in the two strands of the DNA double helix. Bacteria are haploid and repair works great
Term
T or F-Spontaneous depurination and the removal of a deaminated C by uracil DNA glycosylase both leave an identical intermediate, which is the substrate recognized by AP endonuclease.
Definition
True
Term
T or F -The principle function of the SOS response in the E coli is to increase cell survivial by introducing compensating mutations near the site of the original DNA damage.
Definition
False. Its job is to relax the fidelity of DNA synt. so that it can proceed past a block. (cell dies if not synt occurs, hence it survives with a mutation)
Term
T or F- All the spontaneous deamination products of the usual four DNA bases are recognizable as unnatural when they occur in DNA
Definition
True
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