DNA Damage and Repair Flashcards
DNA damage can be _____like UV light or radiation. Or ____ such as replication errors
Exogenous
Endogenous
Spontaneous DNA alterations can be caused by ____ damage, ___ attack, or uncontrolled _____
Oxidative
Hydrolytic
Methylation
about 5000 bases are lost due to ____ per cell per day
About 100 bases are ____ per cell per day
Depurination
Deamination
Nucleotide oxidation is caused by ___ ___ species. They contain free ___
Reactive oxygen
Radicals
ROS causes ____ of proteins and ___ degradation
Oxidation
Enzyme
An example of an oxidized base is _____
8-oxo-dG
____ 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 ____ ____
Oxo-dG
Oxidative stress
Oxo-dG causes ___ transversions in the DNA replication process
G-T
_______ 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
Benzo[a]pyrene
Oxidized
ROS
Bulky adducts
Transversion
_____ of 5methylcytosine generates thiamine, changing the sequence
Deamination
_____ is when the NH2 on a base gets replaced with a double bond to an oxygen
Deamination
_____ is when the entire base gets cleaved from the sugar phosphate backbone, leaving an OH group in its place
Depurination
Deamination creates alternate _____ that are not easily recognized for repair, resulting in ____.
Side note: ____ does not have a Deamination structure
Nucleotides
Mutations
Thymine
If a _____ occurs, the base pair is still there, but incorrect from the parent strand
If _____ occurs, the base is deleted
Deamination
Depurination
Alterations that affect two or more bases:
____ dimers
DNA ______
DNA double strand ____
Pyrimidine
Cross links
Breaks
____ _____ 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
Pyrimidine dimer
UV Light
Blocks
_____ ____: 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
Intrastrand cross link
Interstrand crosslink
Alkylating agents
Cross links are used in ____
Chemotherapy
DNA _____ ____ breaks are caused by ionizing irradiation and oxidative free radicals. It is considered the most ____ type of DNA damage. It can cause _____
Double strand
Deleterious
Translocations
DNA damage is the primary cause of ____ that kill 500,000 Americans yearly and cost $100 billion per year
Cancers
Unrepaired DNA damage contributes to ___ but also ____ and genetic ___
Aging
Evolution
Diversity
Most DNA repair mechanisms are conserved from _____ to human. The most precise repair pathways use the undamaged homologous chromosome, sister chromatid, as a ____
Bacterium
Template
____ ____ ____ is central to many fundamental processes in cells and organisms
DNA damage response (DDR)
In a diseased cell the rate of DNA ____ is greater than the rate of ____
Damage
Repair
Cancer incidence increases with ____. Mutations accumulate and DNA repair efficiency decreases
Age
____ ____ 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
Base excision
Glycosylases
____ ___ 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
Nucleotide excision
Distorted
Endonuclease
____ ____ repair uses ____ and ___ to scan the DNA and remove the damage
DNA mismatch
MutS
MutL
____ ____ ____ ____ repair detects loss of nucleotide due to degradation from ends. Damage repaired accurately using information from ____ ____
DNA double strand break
Sister chromatid
____ ____ is used in double strand break repair
Homologous recombination
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
Cell cycle
ATM
Ataxia-telangiectasia (AT)
____ 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
P53
Arrest
Cyclin dependent kinase (CKI)
_____ cancers are often caused by defects in DNA repair genes
Inherited
____ ____ is caused by the MLH1 mismatch repair defect inherited in a hereditary nonpolyposis colorectal cancer
Lynch syndrome
____ _____ 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
Xerodedma pigmentosum (XP)
XP mutations are found in genes that mediate _____ ____ repair such as exonucleases
Nucleotide excision
Large scale DNA damage in almost all cases cannot be ____
Repaired
______ depicts multiple copies of chromosomes often with chromosomal fusions, this is common in advanced cancers
Medulloblastoma
Aneuploidy caused by Nondisjunction events usually result from defects in the ____ ____ checkpoint
Mitotic spindle
Mitotic spindle checkpoint overview:
_____ drugs target cells that replicate and divid. Other fast replicating cells in the body include ____, ____, and ___ ___
Chemotherapeutic
Bone marrow, hair, digestive tract
_____ is decrease production of blood cells
_____ is hair loss
_____ is inflammation of the lining of the digestive tract
Myelosuppression
Alopecia
Mucositis
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
Alkylating agents
Antimetabolites
Anthracyclines (antibiotic)
Plant alkaloids
Topoisomerase inhibitors
Direct gene mutation may generate a new ____ domain in a protein, leading to gene evolution
Functional
Gene duplication and divergence: generates two genes with different ____. ____ are genes with new function in the same species
Functions
Paralogs
_____ 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 —> ____ ____
Transposition
Transposons
Genetic diversity
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
Intragenic
Duplication
Segment shuffling
Horizontal
I-small genetic variation: ___ base pair exchanges
Single
II-medium genetic variations: ____ or ____
Insertions or deletions
III-large genetic variations: ____ ____
Structural rearrangements
Point mutation is a ___ base pair exchange
Single
____ ___ is a point mutation that does not affect the amino acid sequence, no change in the amino acid chain
Silent mutation
____ ____ is a point mutation that results in one amino acid being replaced by another
Missense mutation
____ ___ is a type of point mutation that results in the codon for a stop codon, premature termination
Nonsense mutation
single nucleotide polymorphisms (SNPs) are associated with conditions such as ___ ____, ___, and ____ but interestingly are mostly found ____ of coding regions
Heart disease
Asthma
Diabetes
Outside
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 ___
Insertion
Deletion
3
Cystic fibrosis is caused by a ____ codon deletion. Deletion of the three nucleotides that code for ____. Protein folds improperly, gets degraded
Single
F508
____ ____ ____ 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 ____
Copy number variant (CNV)
Schizophrenia
Cardiovascular
Dosage
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
Tandem repeats
Within
Tri-nucleotide repeat
Generation of unequal tandem sequence arrays:
Homologous recombination and non-homologous End-joining are the two main causes of ____ ____ genetic variations
Large structural
____ that happen between nonhomologous chromosomes can cause cancer, disease, and cell death
Translocations
Answer: it depends
D
