Deck 35: Chromatin: DNA Structure and Replication

Question 1

When dividing cells are progressing through the cell cycle, many checks are imposed to ensure that the process is occuring with fidelity. A critical checkpoint in the cell cycle occurs in response to DNA damage, such as that induced by UV light. Which of the following cell-cycle proteins is involved in DNA damage-mediated cell-cycle arrest?

A) CDK2
B) cyclin A
C) cyclin D
D) E2F
E) p53

Answer 1

p53

Question 2

You are carrying out experiments to study DNA replication in a cell line derived from a breast cancer tumor. You discover that the replication process does not completely copy all of each chromosome. Examination of the process using electron microscopy indicates that replication ceases near to where the DNA strands are attached to the chromatin scaffold. Given these observations, which of the following activities is most likely to be defective in these cells?

A) DNA ligase
B) helicase
C) polymerase-α
D) single-stranded binding proteins
E) topoisomerase

Answer 2

topoisomerase

Question 3

You are involved in a clinical study aimed at examination of effects of telomere length on aging and disease. You experimentally determine the length of telomeric repeats in children and adults, including both groups with individuals of normal development and abnormal development. In addition, you have included a group of individuals suffering various cancers. Which of the following observations would most closely reflect the findings of your study?

A) longer telomeres in all the abnormal groups
B) longer telomeres in developmentally disabled and cancer groups
C) shorter telomeres in the older group and the developmentally disabled group
D) shorter telomeres in the older group only
E) shorter telomeres in only the young and developmentally normal individuals

Answer 3

shorter telomeres in the older group and the developmentally disabled group

Question 4

You are treating a child who presents with short stature, hypotonia, small hands and feet, obesity, and mild to moderate retardation. An analysis for genomic anomalies reveals a deletion in chromosome 15 and it is determined that this deletion came from the paternal genome. The symptoms and genetic data indicate the child is suffering from which of the following disorders?

A) Angelman syndrome
B) Ataxia telangiectasia
C) Beckwith-Wiedemann syndrome
D) Prader-Willi syndrome
E) Rett syndrome

Question 5

The camptothecins are an alkaloid class of anticancer drugs used in the treatment of colon and breast cancers. These compounds function by inhibiting the activity of which of the following enzymes?

A) ATP-dependent DNA helicase
B) DNA ligase
C) DNA polymerase
D) histone deacetylase
E) topoisomerase I

Question 6

Addition of 5-azacytidine to cultures of growing cells would be expected to result in which of the following?

A) decreased mutagenesis
B) hypermethylation
C) hypomethylation
D) increased mutagenesis
E) inhibition of replication

Question 7

Which of the following statements reflects the process by which of the telomeric ends of chromosomes are replicated?

A) a unique DNA molecule serves as the primer for synthesis
B) a unique RNA molecule serves as the template for synthesis
C) short template-independent blocks of DNA are ligated to the ends using a 5′ → 5′ bond
D) telomeres are replicated as short tandem repeated stretches of ribonucleotides instead of deoxyribonucleotides
E) telomeres are replicated in a temple-independent process

Question 8

The anticancer drug, Taxol, has been an effective chemotherapeutic agent in the fight against ovarian cancer. Which of the following represents the mechanism of action of Taxol?

A) binds to the activated form of the RAS protein which in turn interferes with the signaling cascades involving this protein
B) binds to microtubules, which stabilizes them preventing their shortening and interfering with cell division
C) interacts with the tumor suppressor protein (pRB) encoded by the retinoblastoma susceptibility gene inducing its suppressive activity
D) interacts with topoisomerase II preventing its role in DNA synthesis, which effectively terminates replication
E) interferes with steroid hormone receptor interaction with DNA, thus preventing the growth induction by this class of hormone

Question 9

The term "genomic imprinting" refers to the phenomenon of gene expression dependence on the mode of inheritance. A typical example of this phenomenon is the control of the expression of the growth factor IGF-II. Genomic imprinting is termed "epigenesist," which is defined by which of the following?

A) gene expression results from regulated levels
Of DNA methylation
B) gene expression that is restricted to a specific cell lineage
C) gene regulation is exerted by sex-type specific factors
D) genotype differences are not reflected by phenotype differences
E) phenotype differences are independent of genotype variation

Question 10

Many effective anticancer drugs function as such by interfering with processes of DNA replication. The drug, doxorubicin, is useful in the treatment of lymphomas and breast cancers because of its ability to interfere with which of the following enzyme activities?

A) DNA ligase
B) DNA polymerase a
C) primase
D) topoisomerase II
E) uracil N-glycosylase

Question 11

You are carrying out experiments to study DNA replication in a cell line derived from a breast cancer tumor. You discover that the DNA polymerase in these cells incorporates the incorrect nucleotide into the elongating strand approximately once every thousand bases. These errors suggest that the "proof-reading" capacity of the polymerase is defective. This would be indicative of the following processes not being correctly carried out by the defective polymerase?

A) 3′ to 5′ exonuclease activity
B) 5′ to 3′ exonuclease activity
C) insertion of nucleotides in 5′ to 3′ orientation
D) synthesis of ribonucleotide polymers
E) topoisomerase-mediated cleavage of the DNA backbone

Question 12

Which of the following represents the correct composition of a eukaryotic nucleosome core?

A) histone H1
B) one copy each of histone H2A, H3, and H4
C) one copy each of histone H1, H2A, and H2B
D) two copies each of histone H2A, H2B, H3, and H4
E) two copies each of histone H1, H2A, H3, and H4

Question 13

Which of the following relates to the process of DNA replication?

A) is semiconservative
B) must begin with an incision step
C) requires a primer in eukaryotes but not in prokaryotes
D) requires only proteins with DNA polymerase activity
E) uses 5′→3′ polymerase activity to synthesize 1 strand and 3′→5′ polymerase activity to synthesize the complementary strand

Question 14

An alteration in the structure of topoisomerase II that maintained its functional activity but prevented the action of inhibitory compounds would render useless the action of which of the following chemotherapeutic agents?

A) alkylating drugs
B) anthracyclins
C) antimetabolites
D) camptothecins
E) taxanes

Question 15

The activation of histone deacetylases would be expected to have which of the following effects on DNA replication?

A) decreases the rate
B) destabilizes the double-helix allowing access for polymerases
C) enhances formation of new chromatin following completion of replication
D) increases the rate
E) will have no effect on replication activity

Question 16

Which of the following class of compounds is known to inhibit topisomerse II and thus have shown utility as cancer chemotherapeutics?

A) anthracyclins
B) antimetabolites
C) camptothecins
D) taxanes
E) vinca alkaloids

Question 17

Genomic imprinting is termed "epigenesist," which is defined by which of the following?

A) gene expression results from regulated levels of DNA methylation
B) gene expression that is restricted to a specific cell lineage
C) gene regulation is exerted by sex-type specific factors
D) genotype differences are not reflected by phenotype differences
E) phenotype differences are independent of genotype variation

Question 18

In analyzing a sample of double-stranded DNA, it has been determined that the molar amount of adenosine is 20%. Given this information, what is the content of cytidine?

A) 10
B) 20
C) 30
D) 40
E) 60

Question 19

Chromatin remodeling is associated with alterations in the transcriptional activity of genes in the region of the remodeling. Which of the following statements is most correct concerning the events of chromatin remodeling?

A) chromatin remodeling occurs predominantly in regions enriched in CpG dinucleotides
B) histone acetylation tends to destabilize chromatin structure
C) methylation of guanine residues induces the remodeling event
D) methylation of histone H1 is sufficient to stimulate remodeling
E) remodeling is necessary to induce the property of genomic imprinting

Question 20

Genomic imprinting is a mechanism by which gene expression is regulated. Which of the following correctly defines this mechanism?

A) activation of expression by hypermethylation of genomic DNA sites
B) activation of expression by hypomethylation of genomic DNA sites
C) expansion of trinucleotide repeats in imprinted genes resulting in regulated expression
D) inhibition of expression by hypomethylation of genomic DNA sites
E) regulated expression dependent upon parental origin of regulated gene

Question 21

Telomerase is the specialized activity that allows for replication of the telomeric ends of the chromosomes. In addition to an RNA that is complimentary to the telomeric repeat sequence what other component is required of this complex for its normal activity?

A) DNA-dependent DNA polymerase
B) DNA-dependent RNA polymerase
C) DNA helicase
D) RNA-dependent DNA polymerase
E) RNA-dependent RNA polymerase

Question 22

The cyclin D-CDK4/6 complex is involved in the regulation of progression through the G1 phase of the cell cycle. Which of the following represents a major target of this kinase complex?

A) cyclin E-CDK2
B) E2F
C) p27
D) p53
E) pRb

Question 23

You are examining the efficacy of a new potential anticancer drug. Addition of this drug to rapidly dividing cancer cells results in a blockade to progression through M-phase and the cells arrest at metaphase in the cell cycle. You determine that the drug targets a specific regulatory protein of cell cycle progression and show that it is which of the following proteins/complexes?

A) anaphase-promoting complex
B) cyclin D-CDK4/6
C) cyclin E-CDK2
D) E2F
E) securing

Question 24

You are carrying out experiments designed to ascertain the defect in a cell line derived from a breast cancer tumor. Your studies show that these cells likely arose due to an inability to control progress through the cell cycle in the presence of DNA damage. Exposure of the cells to a dose of γ-irradiation results in a significant propagation of mutated nucleotides into the DNA of daughter cells. Given these observations, which of the following proteins/complexes is most likely defective in your study cell line?

A) anaphase-promoting complex
B) CDK4/6
C) cohesin
D) p53
E) pRB

Question 25

The tumor suppressor pRB functions in the cell cycle by regulating progression from G1 to S-phase. In a cell line derived from a colon carcinoma it is found that the activity of pRB is defective. Which of the following proteins is most likely to be hyperactive in these tumor cells as a consequence of the defective function of pRB?

A) anaphase-promoting complex
B) E2F
C) p21
D) p53
E) securin

Question 26

Control of specific steps in the cell cycle can be studied in cell culture by the use of cell fusion experiments. If cells that are currently in S-phase of the cell cycle are fused with cells that are in the G₁-phase of the cell cycle, which of the following would most correctly reflect the process of DNA synthesis?

A) it is induced in the G₁-phase nucleus
B) it is inhibited in the S-phase nucleus
C) it is stimulated in the S-phase nucleus
D) it is unaffected in the G₁-phase nucleus

Question 27

You are examining a 7-year-old girl brought to you by her parents because they are concerned about the severe skin blistering on her arms and back of her neck a few days after she played in the sun for 15 minutes without sunscreen. Physical examination shows the girl has numerous freckles on her face, neck, arms, and hands. In addition she has numerous telangiectasias on her arms as well as crusty and scaly patches of skin. You suspect the child may have xeroderma pigmentosum. Which of the following processes is most likely to be defective in this child if your diagnosis is correct?

A) DNA polymerase proof-reading activity
B) double-strand break repair during replication
C) photoactivatable thymine dimer removal
D) removal of uracil from DNA
E) reverse transcription of telomeric DNA

Question 28

The anticancer drug etoposide functions because it inhibits the activity of topoisomerase. Which of the following represents the normal function of this enzyme?

A) introduce the primer onto the template of DNA prior to replication
B) remove mismatched nucleotides at the end of replication
C) remove the RNA primer from each Okasaki fragment
D) stabilize single-stranded regions of DNA at the replication fork
E) unwind the DNA duplex during replication

Question 29

RNA and DNA molecules can form doublestranded structures just as in the case of DNADNA duplexes. Given this fact, hybridization of a DNA strand (5′-ACGTC-3′) with which of the following RNA molecules will result in the most stable RNA-DNA duplex?

A) 5′-AGUAC-3′
B) 5′-CAUGA-3′
C) 5′-GACGU-3′
D) 5′-GGCAG-3′
E) 5′-UGCAG-3′

Question 30

You are studying the differences in a particular protein between normal and cancer cells. You find that in the cancer cells the protein is smaller than in the normal cells. Which of the following mutations in the gene encoding the protein would best explain your observations?

A) A to T change in the middle of a long intron in the gene
B) A to T change in the promoter of the gene
C) G to C change in an enhancer found in an intron of the gene
D) missense mutation in the middle of an exon of the gene
E) nonsense mutation in the middle of an exon of the gene

Question 31

Various types of mutations have been found in DNA from damaged, defective, or diseased cells. Which of the following types of mutation will manifest a phenotype only as a consequence of specific circumstances (eg, increased temperature or oxidative stress)?

A) conditional
B) dominant negative
C) gain-of-function
D) lethal
E) null

Question 32

Environmental factors can result in the incorporation of mutations into DNA. Many mutagenic compounds and various forms of radiation lead to mutations through the activity of an error-prone DNA repair mechanism. Which of the following causes mutations by the process of dimerization of adjacent pyrimidines?

A) 5-bromouracil
B) hydroxylamine
C) nitrous acid
D) γ-radiation
E) ultraviolet light

Question 33

Within human chromosomes there are regions of highly concentrated GC content. Many of the cytosine residues that fall within CpG dinucleotide sequences are methylated at the 5 position (m⁵CpG). Which of the following best explains why these methyl-CpG sequences are exceptionally prone to mutation?

A) deamination of m5C produces T
B) histones bind less tightly to m5C sequences than to other sequences
C) homologous recombination occurs preferentially at m5C sequences
D) methylation of C directly changes its basepairing properties
E) methylation of C directly interfere with basepairing during DNA replication

Question 34

Which of the following is the major role of the 3′→5′ exonuclease activity of DNA polymerases?

A) cleaving Okasaki fragments
B) elongating DNA strands
C) excision of RNA primers
D) excision of thymine dimers
E) removing mismatched nucleotides

Question 35

You have isolated a gene that spans a total of 1800 nucleotides. The gene contains 400 nucleotides within 4 exons and 900 nucleotides are associated with the 3 introns. In addition there are 500 nucleotides associated with the regulatory sequences of the gene. Given this information, which of the following numbers most likely represents the number of amino acids encoded by this gene?

A) 130
B) 260
C) 400
D) 800
E) 1200

Question 36

You are studying the characteristics of retroviral integration and replication in mouse cells. You find that in your cells the integrated retroviral genome is highly methylated and transcriptionally inactive. Given these findings, it is most likely that the retrovirus integrated into which of the following chromosomal structures?

A) euchromatin
B) heterochromatin
C) polytene DNA
D) puffed DNA
E) satellite DNA

Question 37

Reverse transcriptase is a specialized form of polymerase. Which of the following most correctly describes the function of this special polymerase?

A) 3′ → 5′ synthesis of DNA from an RNA template
B) 5′ → 3′ synthesis of DNA from an RNA template
C) 3′ → 5′ synthesis of RNA from a DNA template
D) 5′ → 3′ synthesis of RNA from a DNA template

Question 38

The final step in the maturation of the newly synthesized lagging strand of DNA is the formation of phosphodiester bonds between the Okazaki fragments. Which of the following enzymes catalyzes this reaction?

A) DNA polymerase
B) helicase
C) ligase
D) primase
E) topoisomerase

Question 39

The octomeric core of histones provides a structural framework for which of the following complexes?

A) ciliary axonemes
B) endosomes
C) mitochondrial ribosomes
D) nucleosomes
E) the fibrillar region of the nucleus

Question 40

Functional eukaryotic chromosomes contain stretches of DNA harboring specialized nucleotide sequences. Which of the following represents the type of DNA sequence that prevents the strands from becoming shorter with each replication cycle?

A) centromere
B) intron
C) kinetochore
D) replication origin
E) telomere

Question 41

You are carrying out experiments examining the DNase I digestion results in nuclei isolated from several different mammalian cells. Your results show that there is preferential digestion of a set of unique DNA sequences in each cell type. Which of the following characteristics of chromatin in these sequences best explains your observations?

A) deletion of the centromeric DNA
B) incorrect assembly into nucleosomes
C) presence of mutated base pairs
D) transcriptionally active
E) translocation to the nucleus