DNA Damage and Repair

DNA damage repair is highly efficient and the integrity of the genome is maintained
by several high fidelity repair mechanisms. These repair mechanisms are
constitutively expressed and are constantly on guard against a great variety of types
of DNA damage. If an event occurs leading to a large amount of DNA damage,
special emergency repair mechanisms are induced to rapidly repair the damage. These
mechanisms are lower fidelity and are prone to making more mistakes during repair.
This can lead to mutations, aging, genomic instability, cancer and eventually cell
death.
a. True
b. alse
Thymine dimers in DNA are induced by!
a. UV light
b. Intercalation of carcinogenic hydrocarbons
c. DNA rearrangements
d. Inaccurate repair mechanisms
e. "pontaneous deamination of cytosine
#hich of the following is an example of a mechanism for direct reversal of DNA
damage!
a. Photoreactivation
b. "hort patch repair
c. $ong patch repair
d. %ecombination repair
e. &ost'replication "(" repair
)eroderma pigmentosum *)&+ is a genetic disease that leads to a high incidence of
skin cancer. The primary cause of this disease is!
a. aulty replisome control
b. Mutant DNA repair mechanisms for ultraviolet radiation induced
damage
c. A loss of telomerase activity
d. A gain of telomerase activity
e. ,ncontrolled recombination of non'homologous regions of DNA.
The proper order of events for a short patch DNA repair mechanism removing a
erroneously methylated DNA base is!
a. -xonuclease clears damaged region *./0/for 12 to 32 nucleotides+
DNA polymerase fills in the gap *more ./ 0/+ ligase seals the break in
the phosphodiester backbone.
b. Recognition of damage glycosylase removes base endonuclease
cuts DNA strand ! "# bases $% of the lesion e&onuclease clears
damaged region '$%(%for "# to # nucleotides) DNA polymerase fills
in the gap 'more $% (%) ligase seals the brea* in the phosphodiester
bac*bone
c. %ecognition of damage glycosylase removes base endonuclease cuts
DNA strand 3 4 12 bases ./ of the lesion exonuclease clears damaged
region *./0/for 12 to 32 nucleotides+ ligase seals the break in the
phosphodiester backbone
d. %ecognition of damage glycosylase removes base endonuclease cuts
DNA strand 3 4 12 bases ./ of the lesion ligase seals the break in the
phosphodiester backbone
e. $igase breaks the phosphodiester backbone %ecognition of damage
exonuclease clears damaged region *./0/for 12 to 32 nucleotides+ DNA
polymerase fills in the gap *more ./ 0/+ $igase reseals the DNA
backbone.
aulty recombination repair of DNA damage can lead directly to!
a. &oint mutations
b. 5ypermethylation of 6p7 rich regions
c. +hromosome translocations
d. Thymine dimmers
e. Apurinic sites
"("'repair en8ymes!
a. Are low fidelity repair en8ymes that work rapidly to fix damage
b. Are inducible by transcription factors that sense excess DNA damage
c. Are involved in auto'regulatory loops to shut down their expression once
the DNA damage has been repaired.
d. All of the above
e. None of the above.
In humans, p.0 has multiple functions associated with protecting the cells from the
effects of DNA damage. These include all of the below except!
a. 9inding and stabili8ation of single stranded DNA
b. &romoting homologous DNA strand exchange for recombination repair
c. Promotes progression through the cell cycle
d. Acts as a transcription factor inducing the expression of DNA repair
en8yme systems.
e. Acts as an inducer of apoptosis if the DNA damage is too severe
The anti'oncogene product p.0 acts as a transcription factor and induces the
expression of protein, p31, in times of DNA damage emergency. p31 functions to!
a. 9ind to and down regulate cell cycle specific cyclin dependent kinases
b. 9ind &7NA and inhibit its action
c. 9lock the replisome activity : progression, giving time for DNA repair
activity to catch up.
d. All of the above
e. None of the above
There is one origin of replication for each DNA replicon unit. The origin of
replication!
a. Is an A:T rich region
b. 9inds to specific recognition proteins in a cell cycle specific fashion
c. Is rapidly denatured to form secondary DNA structures that recruit
additional proteins *e.g. helicase etc+
d. &rovides a region for the construction of a primosome complex
e. All of the above
The primary functional difference between topoisomerase I and topoisomerase II is
that topo'II!
a. 7uts one strand of DNA and passes the other strand through the break in
order to relax supercoil density.
b. +uts both strands of DNA and passes an entire intact double stranded
DNA segment through the brea* in order to rela& supercoil density
c. 9inds to DNA through non'covalent interactions with serine
d. 7uts DNA only at very specific se;uences like restriction endonuclease
type II
e. None of the above
7iprofloxacin *an antibiotic+, and camptothecan *a phase 0 anti'cancer
chemotherapeutic+, both target the same en8yme system in different organisms. The
target is!
a. The primosome
b. The replisome
c. Topoisomerase activity
d. 5elicase
e. Telomerase
Telomerase is!
a. A riboprotein *%NA < protein+
b. A reverse transcriptase
c. Involved in maintaining the ends of eukaryotic chromosomes
d. Is a target for chemotherapy using si%NA *small inhibitory %NA+
e. All of the above
Two common preservatives found in meats and wines are sodium nitrite and sodium
bisulfite. These preservatives function by preventing bacterial growth, and this is
accomplished by!
a. Inducing strand breaks in DNA
b. ,nducing o&idative deamination of nucleic acid bases 'e.g. cytosine to
form uracil or adenine to form hypo&anthine) leading to mispairing and
point mutations during DNA replication
c. Inactivating DNA repair mechanisms
d. Inducing free radical damage in all type of ma=or biomolecules
e. #ho cares about that> I love bacon and wine>
Doxorubicin has been used to treat leukemia. It blocks the action of DNA and %NA
polymerases. Dox blocks these en8yme activities by!
a. ,ntercalation into the DNA double heli&- disrupting the en.ymes ability
to bind to the DNA.
b. Inserting itself into the active site of these en8ymes as a competitive
inhibitor
c. 9locking the expression of both DNA and %NA polymerase
d. All of the above
e. None of the above
9oth 5untington/s Disease and ragile ) "yndrome are caused by a similar molecular
mechanism leading to very different results! 9oth of these diseases stem from!
a. aulty chromosome break repair
b. aulty recombination repair
c. aulty excision repair
d. Amplification of triple repeats '+A/ or +//) from 0(# to 12#3.
e. 6eneration of microsatellite DNA
A .2 year old woman visits a neurologist regarding weakness and spastic movements in
her lower extremities. An ?%I reveals significant loss of tissue mass in specific regions
of her brain. A diagnosis of 5untington/s Disease is made and genetic tests are ordered.
#hat would the neurologist most likely expect to see in confirming the diagnosis@
a. 7hromosomal translocation
b. "ingle nucleotide polymorphism
c. %estriction length polymorphisms
d. Repeated 'redundant) nucleotide insertions 'triple repeats)
e. %egional nucleotide deletions
?ethylated cytosines *.me7+ in 766 elements can be found in promoter regions from
genes. These are known to be mutational hot'spots because they are not repaired if they
undergo spontaneous oxidative deamination. #5A@
a. 9ecause there are no repair mechanisms in these cells
b. 9ecause the .me7 is converted to .me6 and it looks normal.
c. 4ecause the $me+ is converted to T and it loo*s normal.
d. 9ecause the repair mechanisms are more efficient with damaged purines than
pyrimidines.
e. None of the above
Aou have spent the entire afternoon standing over a smoking charcoal grill cooking food
for the "pring'Term cook'out. In the process, a small amount of both covalent and
intercalation damage to DNA from ben8opyrene has accumulated in both your lungs and
liver. ortunately, you have very efficient DNA damage repair mechanisms for =ust such
occasions. The most likely system to repair a small amount of ben8opyrene induced
damage to DNA is!
a. Direct reversal
b. %ecombination repair
c. "(" repair
d. 5&cision repair 'either short or long patch repair)
e. "trand break repair
The protein, p.0, has been found to be mutated in over half of all cancers, implying that it
has an important role in normal cellular physiology. p.0 functions as!
a. A single stranded DNA binding protein
b. 7ell cycle checkpoint modulator protein
c. A transcriptional factor activating DNA damage repair systems
d. An inducer of apoptosis If damage is too extensive and not repairable
e. All of the above
A B2 year old patient comes to you complaining of fatigue, low grade fever, a persistent
infection. Aou run blood work that indicates an elevated white count with altered
morphology that prompts you diagnose the patient with chronic myelogenous leukemia.
Aou want to perform a test to verify 7?$ with the presence of the &hiladelphia
7hromosome, so youC
a. 6o DI"5ingE*fluorescent in sitiu hybridi8ation+ for t*F!33+ chromosomal
translocation rearrangement
b. $ook for 97%'A9$ fusion products by "outhern hybridi8ation
c. &erform a &7% on expected 97%'A9$ fusion product m%NA expression
d. "ee if the patient responds to 6leevec.
e. All of the above can verify a translocation too* place
The &hiladelphia 7hromosome is the result of a translocation between!
a. Two chromosomes discovered in &hiladelphia
b. %ecombination prone sites on 7hromosomes F and 33
c. The 9cr and Abl genes on two separate chromosomes.
d. All of the above
e. None of the above
7hronic myelogenous leukemias can be treated with a compound called 6leevec.
6leevec works by!
a. 9inding to the active site of 97% serine:threonine kinase
b. 9inding to the active site of A9$ tyrosine kinase
c. 4inding only to the active site of the hybridi.ed 4+R6A47 gene product
d. 9inding to the &hiladelphia 7hromosome and prevent expression of the
mutant hybridi8ed gene product
e. Inducing hyperphosphorylation activity with the tumor cell causing it to
metabolically burn itself out.
A 3. year old male patience is diagnosed with testicular cancer. 5is physician begins an
immediate course of treatment that includes the drug camptothecan, an inhibitor of
topoisomerase, with the intent of blocking DNA synthesis in rapidly growing cancer
cells. #hat is the normal function of this en8yme@
a. 9inds to and stabili8es single stranded DNA
b. Rela&es increased supercoil density upstream of replication for*s.
c. ,nwinds double stranded DNA during replication
d. &romotes the action of lagging strand (ka8aki synthesis
e. %emoves the %NA primers ad=acent to (ka8aki fragments