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2014 FHB Task-oriented Learning Objectives WEEK 1



FHB-2 Human Evolution (Varki)
LO 2-1. Describe the evolutionary relationships of primates, great apes, hominids, and hominins.
LO 2-2. Contrast the likely time of emergence of a striding bipedal gait (upright walking as some running) versus
sustained running ability in hominins, and list three common examples of negative medical consequences
of bipedalism.
LO 2-3. Explain the term cephalo-pelvic disproportion and its medical consequence in Homo sapiens; briefly
explain the major source of the disproportion present in hominins 3 mya that began this difficulty, and
the second disproportion that has increased the difficulty significantly in modern humans.
LO 2-4. Correlate the most likely time of emergence of large brain size, hunting and meat eating and use of stone
tools with either emergence of bipedal posture or sustained running ability.
LO 2-5. Name two hominin species that co-existed with modern Homo sapiens.
LO 2-6. Briefly contrast the usefulness of the US Federal definition of race vs percentage geographic ancestry in
reflecting genetic heredity, and appreciate how this definition of race might affect disease statistics.
LO 2-7. Explain the basis of natural selection, describe the source of most of the common human diseases and list
two reasons the slowness of natural selection contributes to disease.
LO 2-8. List and correct common fallacies concerning the effects of biological evolution on: i) selection
optimizing a species, ii) pathogen evolution, iii) health and longevity, and iv) aging.
LO 2-9. Briefly explain the genetic basis of human variation in skin color, lactose tolerance and alcohol
intolerance.
LO 2-10. Briefly describe the hygiene hypothesis and identify one disease correlated with it.
LO 2-11. Define the time period of the environment of evolutionary adaptation (EEA) of humans and contrast
human diet during the EEA with modern Western diet.
LO 2-12. Identify four diseases correlated with the thrifty gene hypothesis and briefly explain the evolutionary
rationale for this hypothesis.

FHB-3 Cancer Etiology (Millard)
LO 3-1. Use destruction (or not) of normal tissue to distinguish between localized tumor growth by benign
tumors versus tissue invasion by malignant tumors; distinguish tissue invasion from metastasis; compare
and contrast the features of benign tumors, malignant tumors and normal cell growth.
LO 3-2. Correlate carcinomas, sarcomas, lymphomas and leukemias with the cell type of origin for each.
LO 3-3. For sporadic cancers (no known inherited predisposition) and cancers with inherited predisposition:
a. Contrast the frequencies of sporadic cancer versus cancers with inherited predisposition.
b. Correlate inheritance being single gene versus polygenic for i) inherited cancer syndromes, ii)
syndromes of defective DNA repair, and iii) familial cancers
c. Contrast the features typical of familial cancers versus sporadic cancers
LO 3-4. Identify the general process common to many pre-neoplastic conditions, and correlate a specific pre-
neoplastic condition with i) endometrial carcinoma, ii) colon carcinoma, iii) liver cancer, and iv) skin
cancer; briefly explain whether or not pre-neoplastic conditions always cause cancer.
LO 3-5. For chemical carcinogenesis:
a. Distinguish between direct acting and indirect acting agents and give an example of each.
b. Define mutagen and describe the relationship between carcinogens and mutagens.
c. Distinguish between the mechanism of initiators and promoters and their roles in carcinogenesis.
d. List promoters for head and neck squamous cancers, endometrial cancers and colorectal cancer, and
note which is also considered a pre-neoplastic condition.
e. Name the category (type) of enzymes that most commonly convert indirect acting agents.

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LO 3-6. For radiation carcinogenesis: (this LO integrates with FHB Lecture 8 Mutagenesis and DNA Repair)
a. Describe the type of DNA damage caused by ionizing radiation that makes it a mutagen, and identify
the two tissues most sensitive to this mutagenesis and carcinogenesis.
b. Describe the type of DNA damage caused by UV radiation that makes it a mutagen, and identify two
types of skin cancer associated with UV exposure.
c. Identify the DNA repair system that repairs DNA damage caused by UV radiation, and name the
disease cause by an inherited deficiency of this repair.
LO 3-7. For microbial carcinogenesis:
a. For human papilloma virus (HPV):
i. Name a type of benign tumor and a type of cancer associated with low-risk vs high-risk subtypes.
ii. Describe the roles of viral DNA integration and viral proteins in carcinogenesis by HPV.
iii. Briefly explain why a Pap smear is the most successful cancer screening test.
b. Briefly explain the mechanism by which Epstein Barr virus (EBV) promotes B-cell lymphoma.
c. Name two viruses responsible for >2/3 of liver cancer and their general contribution to carcinogenesis
d. Name the bacteria that is the main cause of peptic ulcers and is a carcinogen for gastric carcinoma
LO 3-8. Describe conceptually how the accumulation of mutations in a cell can lead to cancer and how this
correlates with the statement that non-lethal genetic damage lies at the heart of carcinogenesis.

FHB-4 Cell Structure and Function (Novick)
LO 4-1. Identify the plasma membrane, the cytosol and each of the following membrane-bound organelles on an
unlabeled cell diagram and on a unlabeled transmission electron micrograph of a mammalian cell:
a) endoplasmic reticulum b) Golgi complex c) lysosomes d) mitochondria
e) nucleus f) peroxisomes
LO 4-2. For the membrane-bound organelles:
a) List three molecular processes that occur in the nucleus and the route by which proteins and RNAs
move into and out of the nucleus.
b) Name three destinations of proteins synthesized on the rough endoplasmic reticulum and briefly
describe the role the Golgi apparatus plays in determining the destination of each protein.
c) Briefly describe the function of lysosomes and of endosomes.
d) In a diagram of a mitochondrion, label two compartments, two membranes, and the location of the
electron transport chain and ATP synthase.
e) List a function of peroxisomes.
LO 4-3. Fill in the table of the specific specialized features of the listed cells, e.g., abundance of specific
organelles, lipid droplets or granules, plasma membrane specializations and their basic function,
cytoskeletal specializations and their basic function.
Cell type Specific specialized features correlated with function
adrenal gland steroid secreting cell
endocytic cells
endothelial cell
intestinal epithelial cell
pancreatic acinar cell
red blood cell
skeletal muscle fiber
sperm
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a) recognize each cell from a diagram or transmission electron micrograph and label the specialized
features that correlate with its function.
b) identify the specialized cell and its function from a description of the cell features.
LO 4-4. For intestinal wall tissue and tracheal wall tissue:
a. Identify epithelial cells, endothelial cells, and muscle within a diagram or microscopic image
b. Describe the contribution of each cell type to intestinal or tracheal function
c. Identify and correlate cilia and microvilli with the appropriate cell types in each tissue.
LO 4-5. Identify the organelle whose dysfunction in neurons results in in Tay Sachs disease, name the specific
enzyme deficiency and the enzyme substrate whose accumulation results in brain damage.

FHB-5 Chromosomes and DNA (Holm)
LO 5-1. Identify the feature that distinguishes
purine from pyrimidine nucleotides and
identify the purine and pyrimidine
nucleotides in the diagrams at right; for
any one nucleotide: i) label the sugar and its ring oxygen, ii) label each sugar carbon by number, iii)
identify the carbon and chemical group that would distinguish deoxynucleotides from ribonucleotides, iv)
label the phosphate group, and v) label the 3 and 5 ends of the nucleotide.
LO 5-2. List a base pair with three hydrogen bonds in DNA and in RNA; list a base pair with two hydrogen bonds
in DNA and in RNA.
LO 5-3. List a difference between DNA and RNA in their polymeric structure, in their sugars and in their bases.
LO 5-4. Describe the chemical groups on each of two deoxynucleotide triphosphates involved in the formation of
a phosphodiester bond (to form a dinucleotide).
LO 5-5. Describe the role of antiparallel strands and base complementarity in a double-stranded DNA helix and in
the local helical regions of single-stranded RNA that form when the RNA folds back on itself.
LO 5-6. On an unlabeled outline diagram of DNA that uses the same nucleotide structures as in LO 5-1:
a) label a bond: i) formed by a polymerase, ii) broken by a helicase, and iii) broken by a glycosidase.
b) label the 5 and 3 end of each strand and explain the feature that identifies each, and
c) identify the DNA sequence of each strand based on base size and hydrogen bonds between base pairs
LO 5-7. List Chargaffs four rules of DNA base composition and briefly explain the rationale for each; apply these
rules in the analysis of experimental base composition data.
LO 5-8. Briefly explain the cause of DNA supercoiling and describe the basic function of topoisomerases; list a
clinical use for inhibitors of i) eukaryotic topoisomerase, and ii) prokaryotic topoisomerase (gyrase), and
provide a brief rationale for each clinical use.
LO 5-9. Recognize the centromere and telomeres on a simple chromosome diagram, and describe the basic
functions of centromeres and telomeres.
LO 5-10. Describe the components and structural features of a nucleosome; define chromatin; describe
euchromatin and heterochromatin and the potential for transcription of genes within each form.
LO 5-11. Of 2 nm, 11 nm, 30 nm, 300 nm and 700 nm, indicate the size category that best corresponds to/is the
most common or prominent size category for: a) beads on a string chromatin, b) chromatin during
mitosis, c) chromatin containing loops in an extended form, d) chromatin with nucleosomes but no
other protein, e) DNA with no protein, and f) unperturbed euchromatin.
LO 5-12. Contrast the features of epigenetic and genetic heritability, and describe: i) an epigenetic modification
of DNA and ii) epigenetic modifications of nucleosome proteins.



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FHB-6 DNA Replication and Viruses (Spector)
LO 6-1. Contrast the major enzyme/complex, the template and product for each of the three major processes
involved in the central dogma of molecular biology,
LO 6-2. List the direction all polymerases read the template strand briefly explain why nucleic acids can only be
synthesized from 5 to 3; describe the distinguishing feature of semi-conservative DNA replication.
LO 6-3. For DNA and RNA polymerases (prokaryotic and eukaryotic), compare and contrast:
a. the substrates used by each, and the chemical group that differentiates these substrates
b. whether a primer is required for initiation or if initiation can occur de novo (no primer)
c. if the polymerase has a proofreading activity, and name the enzymatic activity that provides this
LO 6-4. For eukaryotic DNA synthesis initiation, name: i) the DNA sequence at which it occurs, ii) the protein
that recognizes that site, and iii) two enzymatic activities required for initiation.
LO 6-5. Name the cell cycle phase during which DNA synthesis occurs, define licensing, name the key protein
and key complex involved in licensing, and describe the general function of the key protein.
LO 6-6. Use the listed choices to correlate geminin and the complexes at origins during the cell cycle phases.
For geminin: bound at origin after single initiation or bound at origin or low level, not bound at origin
For complex: active replication complexes or no complex at origin or pre-replication complex origin or
Cell cycle Geminin Complex
G1 (after M)
During S
G2
LO 6-7. For eukaryotic DNA elongation:
a. identify the features of DNA replication that require the presence of both a leading and lagging strand
at each replication fork
b. draw a linear diagram of eukaryotic DNA partway through elongation with two replication forks, and
label each of the following:
i. 3 and 5 ends of each strand, the origin sequence, and the direction of movement of each fork
ii. each leading strand and its primer
iii. the Okazaki fragments of each lagging strand and the primer for each fragment
iv. the primer removal and replacement, and ligation of the first two Okazaki fragments of one fork
LO 6-8. Name the eukaryotic replication fork enzymes or complexes that: i) separate the helical strands, ii)
synthesize all primers (two activities), iii) synthesize the leading strand DNA iv) synthesize the Okazaki
fragment DNA, v) remove primers, vi) join Okazaki fragments and leading and lagging strands
together, and vii) is present but inactive in the pre-replication complex (and activated during licensing)
LO 6-9. For i) through vi) in LO 10-8: a) predict whether DNA replication would halt or continue if the activity
were suddenly terminated partway through a round of DNA replication, and ii) describe the effect on
any newly synthesized DNA.
LO 6-10. Briefly describe the contribution of parental and new histone dimers to nucleosome formation after
the replication fork, and integrate with lecture 6 (Control of Transcription) to predict its role in
maintaining epigenetic histone modifications after cell division.
LO 6-11. Briefly describe the ends problem for linear DNA, how telomeres provide a solution for eukaryotes,
and the structural feature that protects the short ssDNA overhang on each telomere from degradation.
LO 6-12. Draw a linear diagram of one end of a double-stranded DNA telomere with a short 3 overhang,
labeling 5 and 3 strand ends, and diagram extension of both strands of the telomere, including:
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i. two cycles of 3 strand extension by telomerase, labeling the 3 and 5 ends of the TERC RNA and
diagramming the complementary deoxynucleotides added to the 3 DNA strand by the TERC reverse
transcriptase protein of telomerase
ii. synthesis of the 5 telomere strand by and ligase.
LO 6-13. From a description of DNA replication by SV40, Adenovirusvirus, or Herpesvirus, identify whether
the replication is i) semi-conservative or not, ii) uni- or bi-directional, and iii) requires lagging strand
synthesis at each replication fork or not.
LO 6-14. Identify the structural characteristic common to AZT and acyclovir, the type of enzyme inhibited by
these drugs, the viral process inhibited, and how the structural characteristic causes the inhibition.

FHB-7 Histology Lab 1 for MS1s (Calcutt) these will be provided by Dr. Calcutt.

FHB-8 Mutagenesis and DNA Repair (Spector)
LO 8-1. Define mutation, and:
a. briefly explain why somatic mutations are associated with cancer and germ-line mutations are
associated with inherited diseases.
b. list three structural categories of point (single base pair) mutations, note which category includes
transitions and transversions, and explain why nonsense and missense mutations are in this category.
c. list three types of changes in chromosomal segments (containing multiple genes) that cause
chromosomal mutations.
NOTE: Mutations can also categorized functionally by the effect on gene expression due to the regulatory sequences or
codons they disrupt or modify. For example, nonsense and missense mutations are functional categories, not structural.
Frameshift, splice site, pA sequence, enhancer and silencer mutations are also functional descriptions. Using a description
of a mutations effects on mRNA and protein amount/length to identify the mutated gene sequence/codon is a key ability for
answering application questions in molecular biology, as seen in LO MUT3 after the Protein Synthesis lecture in Week 2.
LO 8-2. List four types of chemical modifications that can damage single nucleotides, and name the type of
mutation caused by DNA replication in the presence of a tautomeric shift in a base.
LO 8-3. For radiation-induced DNA damage, note whether the damage causes significant structural distortion of
the DNA helix, and describe the type(s) of DNA damage that result from:
a. ionizing radiation (e.g., X-rays or gamma rays)
b. UV radiation, including the specific bases affected and the types of bonds involved
LO 8-4. For chemical mutagens, name the:
a. type of damage done to a base by nitrous acid, how this can result in deoxyuracil, and the type of
structural mutation that results from DNA replication in the presence of that damage.
b. base most commonly methylated by products of cellular metabolism and its effect on the helix.
c. base most commonly oxidized by products of cellular metabolism and its effect on the helix.
d. type of DNA damage that results from Cis-platinum chemotherapy
LO 8-5. For the eukaryotic signal for help (aka DNA damage checkpoint described in Control of Cell
Cycle), list the sequence from DNA damage to repair, including ATM, p53 and halting the cell cycle.
LO 8-6. Name the enzymatic activity responsible for proofreading by DNA Polymerase and , and predict a
structural type of point mutation that would be increased in its absence.
LO 8-7. For double-stranded DNA break repair, name:
a. the type of repair that can occur throughout the cell cycle and the type of mutation this repair causes.
b. the accurate repair that can occur in late S or in G2, the source of sequence information that allows
this repair to be accurate, and how this source correlates to the cell cycle phases the repair is active
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c. the repair using BRCA1/2; briefly explain why BRCA deficiency increases the risk of cancer.
LO 8-8. For mismatch repair (MMR):
a. name the Pol error that results in a mismatch or in a single-stranded DNA loop, and predict the
structural mutation each will cause if replication occurs again before repair
b. list ligase, nucleases and Pol in the correct sequence for repair.
c. name the type of cancer that an MMR deficiency predisposes to, and briefly explain why these
particular tumors are resistant to Cisplatin chemotherapy.
LO 8-9. For direct repair, i) name the active protein and ii) name the DNA damage it recognizes and repairs.
LO 8-10. For base excision repair (BER):
a. name three different chemically-damaged bases from LO 8-4 that can be recognized by different
BER glycosidases
b. list AP endonuclease, DNA Pols, glycosidase, and ligase in the correct sequence for the repair.
c. name the type of damage to which PARP recruits BER to accurately repair; name the type of damage
generated if DNA replication prior to repair, and briefly explain why inhibiting PARP in a tumor
lacking BRCA activity could be expected to kill those tumor cells (see slide 11-5).
LO 8-11. For nucleotide excision repair (NER),
a. name a damage recognized by NER proteins, and briefly describe how the XP recognition proteins of
GG-NER and how the CSA/CSB recognition proteins of TC-NER each recognize the damage.
b. list ligase, Pol and XP nucleases in the correct repair sequence initiated by either recognition.
c. name the disease resulting from XP protein deficiency and name the type of cancer that occurs.
LO 8-12. List the three types of DNA repair that involve excision and replacement of the damaged nucleotide or
nucleotide sequence, and name the source of the sequence information they all use to ensure accuracy.
LO 8-13. For translesion DNA synthesis (translesion repair), briefly explain: i) the effect of UV damage in the
DNA on replication fork function, ii) the benefit of recruiting of DNA Pol zeta, iii) whether or not DNA
Pol zeta repairs the original UV damage, and iv) whether or not Pol zeta synthesizes DNA accurately.
LO 8-14. Explain why higher levels of DNA damage can increase reliance on translesion Pol zeta and NHEJ, and
how this reliance increases the risk of cancer.

FHB-9 Control of Transcription (Glass)
LO 9-1. Review LO 5-10 and 5-11, name the complexes that decondense (reposition) nucleosomes in 11 nm
chromatin, list their energy source, and predict their effect on gene transcription.
LO 9-2. Correlate histone acetylation and deacetylation with gene expression level (increased/decreased); name
the histone modification associated with gene silencing and heterochromatin formation; briefly explain
the role of reader and effector proteins in these types of regulation of gene expression.
LO 9-3. Review LO 5-3 and correlate the eukaryotic RNA Polymerases I, II and III with synthesis of their
appropriate RNA products (tRNAs, rRNAs, mRNAs and miRNAs).
LO 9-4. For Pol II transcription of mRNA, name the:
a. category of transcription factors that form the initiation complex with Pol II and the DNA sequence
on which the initiation complex forms
b. category of transcription factors required for regulation of mRNA transcription and the category of
DNA sequences to which they bind
c. type of transcription factor that binds to an enhancer and its effect mRNA initiation,
d. type of transcription factor that binds to a silencer and its effect on mRNA initiation.
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LO 9-5. Briefly explain a reasonable sequence involving core transcription factors, enhancers, histone
acetylating complexes, nucleosome remodeling complexes, Pol II, sequence-specific transcriptional
activators and the promoter in the formation of the initiation complex for mRNA transcription.
LO 9-6. Use histone acetylating complexes and nucleosome remodeling complexes and the description of the
glucocorticoid receptor in a sequence by which cortisol (a glucocorticoid) could increase expression of
a liver cell enzyme.
LO 9-7. Define cell differentiation; integrating with LO 5-13, briefly explain why differentiation of specialized
cell types during development must be mediated by combinations of transcription factors exerting
epigenetic regulation, and cannot be mediated by changes in DNA sequences.
LO 9-8. Name the specific nucleotide modification meant by DNA methylation, and:
a. diagram the double-stranded DNA helix containing the sequence: 5 ACGTACCTCGT3 and label
the nucleotides in each strand potentially be targeted by DNA methylases for epigenetic regulation
b. propose how sequence-specific transcriptional activators and de novo DNA methylases could result in
decreased transcription of a specific gene
c. briefly explain how maintenance methyltransferases (DNA methylases) allow this epigenetic
modification to be maintained after cell division.
d. briefly explain how DNA methylation can lead to gene silencing
Integrative application LOs:
LO 9-9. On the diagram of a typical eukaryotic protein-coding gene below, the arrow indicates the start and
direction of mRNA transcription and the darkest grey boxes are exons:

a. label the:
a) 5 and 3 ends of each DNA strand,
b) template DNA strand read by Pol II and the (complementary) coding DNA strand
c) location of the promoter and the stop transcription sequence
b. number the exons (E-1, E-2, etc.) and introns (I-1, I-2, etc.)
c. indicate two different likely locations for an enhancer and two for a silencer.
LO 9-10. Fill in the table to predict the effect (increased, decreased, none, no change) of each mutation on the
mRNA and protein product expressed from the mutant gene.
Amount of mRNA Length of mRNA

Amount of protein

Length of protein
Deleted enhancer
Deleted promoter
Deleted silencer

LO 9-11. Provide a possible mechanism by which i) DNA methylation can silence gene transcription and ii)
accidental DNA methylation of a tumor suppressor gene (e.g., the protein needed for p53-mediated
apoptosis) could occur and contribute to cancer development.

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