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Fundamentals of Medicine: Exam II > DNA Damage and Repair > Flashcards

DNA Damage and Repair Flashcards

1
Q

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

A

Exogenous
Endogenous

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2
Q

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

A

Oxidative
Hydrolytic
Methylation

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3
Q

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

About 100 bases are ____ per cell per day

A

Depurination
Deamination

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4
Q

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

A

Reactive oxygen
Radicals

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5
Q

ROS causes ____ of proteins and ___ degradation

A

Oxidation
Enzyme

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6
Q

An example of an oxidized base is _____

A

8-oxo-dG

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7
Q

____ 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 ____ ____

A

Oxo-dG
Oxidative stress

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8
Q

Oxo-dG causes ___ transversions in the DNA replication process

A

G-T

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9
Q

_______ 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

A

Benzo[a]pyrene
Oxidized
ROS
Bulky adducts
Transversion

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10
Q

_____ of 5methylcytosine generates thiamine, changing the sequence

A

Deamination

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11
Q

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

A

Deamination

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12
Q

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

A

Depurination

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13
Q

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

A

Nucleotides
Mutations
Thymine

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14
Q

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

If _____ occurs, the base is deleted

A

Deamination
Depurination

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15
Q

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

A

Pyrimidine
Cross links
Breaks

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16
Q

____ _____ 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

A

Pyrimidine dimer
UV Light
Blocks

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17
Q

_____ ____: 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

A

Intrastrand cross link
Interstrand crosslink
Alkylating agents

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18
Q

Cross links are used in ____

A

Chemotherapy

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19
Q

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

A

Double strand
Deleterious
Translocations

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20
Q

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

A

Cancers

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21
Q

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

A

Aging
Evolution
Diversity

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22
Q

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

A

Bacterium
Template

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23
Q

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

A

DNA damage response (DDR)

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24
Q

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

A

Damage
Repair

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25
Q

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

A

Age

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26
Q

____ ____ 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

A

Base excision
Glycosylases

27
Q

____ ___ 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

A

Nucleotide excision
Distorted
Endonuclease

28
Q

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

A

DNA mismatch
MutS
MutL

29
Q

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

A

DNA double strand break
Sister chromatid

30
Q

____ ____ is used in double strand break repair

A

Homologous recombination

31
Q

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

A

Cell cycle
ATM
Ataxia-telangiectasia (AT)

32
Q

____ 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

A

P53
Arrest
Cyclin dependent kinase (CKI)

33
Q

_____ cancers are often caused by defects in DNA repair genes

A

Inherited

34
Q

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

A

Lynch syndrome

35
Q

____ _____ 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

A

Xerodedma pigmentosum (XP)

36
Q

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

A

Nucleotide excision

37
Q

Large scale DNA damage in almost all cases cannot be ____

A

Repaired

38
Q

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

A

Medulloblastoma

39
Q

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

A

Mitotic spindle

40
Q

Mitotic spindle checkpoint overview:

A
41
Q

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

A

Chemotherapeutic
Bone marrow, hair, digestive tract

42
Q

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

A

Myelosuppression
Alopecia
Mucositis

43
Q

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

A

Alkylating agents
Antimetabolites
Anthracyclines (antibiotic)
Plant alkaloids
Topoisomerase inhibitors

44
Q

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

A

Functional

45
Q

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

A

Functions
Paralogs

46
Q

_____ 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 —> ____ ____

A

Transposition
Transposons
Genetic diversity

47
Q

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

A

Intragenic
Duplication
Segment shuffling
Horizontal

48
Q

I-small genetic variation: ___ base pair exchanges

A

Single

49
Q

II-medium genetic variations: ____ or ____

A

Insertions or deletions

50
Q

III-large genetic variations: ____ ____

A

Structural rearrangements

51
Q

Point mutation is a ___ base pair exchange

A

Single

52
Q

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

A

Silent mutation

53
Q

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

A

Missense mutation

54
Q

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

A

Nonsense mutation

55
Q

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

A

Heart disease
Asthma
Diabetes
Outside

56
Q

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 ___

A

Insertion
Deletion
3

57
Q

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

A

Single
F508

58
Q

____ ____ ____ 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 ____

A

Copy number variant (CNV)
Schizophrenia
Cardiovascular
Dosage

59
Q

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

A

Tandem repeats
Within
Tri-nucleotide repeat

60
Q

Generation of unequal tandem sequence arrays:

A
61
Q

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

A

Large structural

62
Q

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

A

Translocations

63
Q
A

Answer: it depends

64
Q
A

D

Fundamentals of Medicine: Exam II (19 decks)

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