DNA Damage and Repair

Question 1

DNA damage can be _____like UV light or radiation. Or ____ such as replication errors

Answer 1

Exogenous
Endogenous

Question 2

Spontaneous DNA alterations can be caused by ____ damage, ___ attack, or uncontrolled _____

Answer 2

Oxidative
Hydrolytic
Methylation

Question 3

about 5000 bases are lost due to ____ per cell per day

About 100 bases are ____ per cell per day

Answer 3

Depurination
Deamination

Question 4

Nucleotide oxidation is caused by ___ ___ species. They contain free ___

Answer 4

Reactive oxygen
Radicals

Question 5

ROS causes ____ of proteins and ___ degradation

Answer 5

Oxidation
Enzyme

Question 6

An example of an oxidized base is _____

Answer 6

8-oxo-dG

Question 7

____ levels increase in the lung in response to inhaling fine particles like smoke, which is associated with cancer and cardiovascular disease. Oxo-dG is used as a marker for ____ ____

Answer 7

Oxo-dG
Oxidative stress

Question 8

Oxo-dG causes ___ transversions in the DNA replication process

Answer 8

G-T

Question 9

_______ is an aromatic polycyclic hydrocarbon and pro-carcinogen produced by cigarette smoke. It is not carcinogenic until it is ____ within a by the action of ____. It then binds covalently to guanine residues in DNA causing the formation of ____ ____, interrupting GC base pairing and distorting helix structure. This usually results in G to T ____ mutation in lung cancer

Answer 9

Benzo[a]pyrene
Oxidized
ROS
Bulky adducts
Transversion

Question 10

_____ of 5methylcytosine generates thiamine, changing the sequence

Answer 10

Deamination

Question 11

_____ is when the NH2 on a base gets replaced with a double bond to an oxygen

Answer 11

Deamination

Question 12

_____ is when the entire base gets cleaved from the sugar phosphate backbone, leaving an OH group in its place

Answer 12

Depurination

Question 13

Deamination creates alternate _____ that are not easily recognized for repair, resulting in ____.
Side note: ____ does not have a Deamination structure

Answer 13

Nucleotides
Mutations
Thymine

Question 14

If a _____ occurs, the base pair is still there, but incorrect from the parent strand

If _____ occurs, the base is deleted

Answer 14

Deamination
Depurination

Question 15

Alterations that affect two or more bases:
____ dimers
DNA ______
DNA double strand ____

Answer 15

Pyrimidine
Cross links
Breaks

Question 16

____ _____ is a covalent link between two thymines or two cytosines on the SAME DNA strand. Caused by ___ ___ exposure. This ____ DNA replication and requires a special DNA translesion polymerase to get across

Answer 16

Pyrimidine dimer
UV Light
Blocks

Question 17

_____ ____: blocks DNA replication but can be passed by translesion polymerase
___ ____: blocks DNA replication, must be removed
Both are induced by ____ ____, such as nitrogen mustard, diepoxybutane, or cisplatin

Answer 17

Intrastrand cross link
Interstrand crosslink
Alkylating agents

Question 18

Cross links are used in ____

Answer 18

Chemotherapy

Question 19

DNA _____ ____ breaks are caused by ionizing irradiation and oxidative free radicals. It is considered the most ____ type of DNA damage. It can cause _____

Answer 19

Double strand
Deleterious
Translocations

Question 20

DNA damage is the primary cause of ____ that kill 500,000 Americans yearly and cost $100 billion per year

Answer 20

Cancers

Question 21

Unrepaired DNA damage contributes to ___ but also ____ and genetic ___

Answer 21

Aging
Evolution
Diversity

Question 22

Most DNA repair mechanisms are conserved from _____ to human. The most precise repair pathways use the undamaged homologous chromosome, sister chromatid, as a ____

Answer 22

Bacterium
Template

Question 23

____ ____ ____ is central to many fundamental processes in cells and organisms

Answer 23

DNA damage response (DDR)

Question 24

In a diseased cell the rate of DNA ____ is greater than the rate of ____

Answer 24

Damage
Repair

Question 25

Cancer incidence increases with ____. Mutations accumulate and DNA repair efficiency decreases

Answer 25

Age

Question 26

____ ____ repair, repairs Depurination, deamination, oxidation, and alkylation. DNA _____ recognize and remove the altered base. Apurinic endonuclease and phosphodiesterase remove the sugar phosphate backbone. DNA polymerase and DNA ligase fill the gap

Answer 26

Base excision Glycosylases

Question 27

____ ___ repair, repairs mostly Pyrimidine dimers. A large complex recognizes the _____ DNA helix. An _____ clips the DNA and a helicase unwinds it and removes the damaged fragment. DNA polymerase and ligase fill in the gaps

Answer 27

Nucleotide excision Distorted Endonuclease

Question 28

____ ____ repair uses ____ and ___ to scan the DNA and remove the damage

Answer 28

DNA mismatch MutS MutL

Question 29

____ ____ ____ ____ repair detects loss of nucleotide due to degradation from ends. Damage repaired accurately using information from ____ ____

Answer 29

DNA double strand break Sister chromatid

Question 30

____ ____ is used in double strand break repair

Answer 30

Homologous recombination

Question 31

Cells can produce DNA repair enzymes in response to DNA damage and DNA damage delays the ____ ___. An important protein in DNA damage signaling is ____ which signals a response to oxygen inflicted DNA damage. Defects in ATM cause ____ ____ disease

Answer 31

Cell cycle ATM Ataxia-telangiectasia (AT)

Question 32

____ is an important G1 checkpoint control gene. Following damage detection, p53 mediates a decision to____ cells in G1 or G2. It increases the transcription of ____ ____ ___ inhibitors. Repair or undergo apoptosis

Answer 32

P53 Arrest Cyclin dependent kinase (CKI)

Question 33

_____ cancers are often caused by defects in DNA repair genes

Answer 33

Inherited

Question 34

____ ____ is caused by the MLH1 mismatch repair defect inherited in a hereditary nonpolyposis colorectal cancer

Answer 34

Lynch syndrome

Question 35

____ _____ is a genetically heterogeneous autosomal recessive disease of defective DNA repair that causes marked sensitivity to UV radiation. Average life span is 30 years. Susceptible to skin cancers

Answer 35

Xerodedma pigmentosum (XP)

Question 36

XP mutations are found in genes that mediate _____ ____ repair such as exonucleases

Answer 36

Nucleotide excision

Question 37

Large scale DNA damage in almost all cases cannot be ____

Answer 37

Repaired

Question 38

______ depicts multiple copies of chromosomes often with chromosomal fusions, this is common in advanced cancers

Answer 38

Medulloblastoma

Question 39

Aneuploidy caused by Nondisjunction events usually result from defects in the ____ ____ checkpoint

Answer 39

Mitotic spindle

Question 40

Mitotic spindle checkpoint overview:

Answer 40

Question 41

_____ drugs target cells that replicate and divid. Other fast replicating cells in the body include ____, ____, and ___ ___

Answer 41

Chemotherapeutic Bone marrow, hair, digestive tract

Question 42

_____ is decrease production of blood cells _____ is hair loss _____ is inflammation of the lining of the digestive tract

Answer 42

Myelosuppression Alopecia Mucositis

Question 43

Cancer drugs: ____ ____: induce DNA cross links ______: interfere with DNA synthesis ________: DNA intercalators that block replication or transcription ____ ___: microtubule inhibitors that block Mitotic cell decision _____ ____: inhibit replication and cause DNA damage

Answer 43

Alkylating agents Antimetabolites Anthracyclines (antibiotic) Plant alkaloids Topoisomerase inhibitors

Question 44

Direct gene mutation may generate a new ____ domain in a protein, leading to gene evolution

Answer 44

Functional

Question 45

Gene duplication and divergence: generates two genes with different ____. ____ are genes with new function in the same species

Answer 45

Functions Paralogs

Question 46

_____ is the movement of mobile genetic elements from one chromosomal site to another. ____ are segments of DNA that can actively jump around the genome through mechanisms that do not involve homologous recombination —> ____ ____

Answer 46

Transposition Transposons Genetic diversity

Question 47

The main driving forces behind gene evolution are: 1. Direct ____ mutation 2. Gene ____ 3. Gene ____ ____: exon shuffling, creates new genes with different domains 4. ___ gene transfer: most common amongst bacteria, conjugation

Answer 47

Intragenic Duplication Segment shuffling Horizontal

Question 48

I-small genetic variation: ___ base pair exchanges

Answer 48

Single

Question 49

II-medium genetic variations: ____ or ____

Answer 49

Insertions or deletions

Question 50

III-large genetic variations: ____ ____

Answer 50

Structural rearrangements

Question 51

Point mutation is a ___ base pair exchange

Answer 51

Single

Question 52

____ ___ is a point mutation that does not affect the amino acid sequence, no change in the amino acid chain

Answer 52

Silent mutation

Question 53

____ ____ is a point mutation that results in one amino acid being replaced by another

Answer 53

Missense mutation

Question 54

____ ___ is a type of point mutation that results in the codon for a stop codon, premature termination

Answer 54

Nonsense mutation

Question 55

single nucleotide polymorphisms (SNPs) are associated with conditions such as ___ ____, ___, and ____ but interestingly are mostly found ____ of coding regions

Answer 55

Heart disease Asthma Diabetes Outside

Question 56

Level II, medium variations: ____ and ____ mutations often causes a frame shift mutation. Can be one or more base pairs. Frameshift will result if it’s not a multiple of ___

Answer 56

Insertion Deletion 3

Question 57

Cystic fibrosis is caused by a ____ codon deletion. Deletion of the three nucleotides that code for ____. Protein folds improperly, gets degraded

Answer 57

Single F508

Question 58

____ ____ ____ is a segment of DNA in which copy-number differences have been found by comparison of two or more genomes. They are associated with ____ and ____ diseases. They can contribute to gene ____

Answer 58

Copy number variant (CNV) Schizophrenia Cardiovascular Dosage

Question 59

Variable number ___ ____ are unique to one individual, used in DNA fingerprinting. However, some tandem repeats are located ____ genes causing fragile X, Huntington’s disease. Caused by _____ ____ expansion

Answer 59

Tandem repeats Within Tri-nucleotide repeat

Question 60

Generation of unequal tandem sequence arrays:

Answer 60

Question 61

Homologous recombination and non-homologous End-joining are the two main causes of ____ ____ genetic variations

Answer 61

Large structural

Question 62

____ that happen between nonhomologous chromosomes can cause cancer, disease, and cell death

Answer 62

Translocations

Question 63

Answer 63

Answer: it depends

Question 64

Answer 64

D