BIOC 205 Lecture 4 Flashcards

Terms Definitions
Base excision repair removes----- generated by ----
Abnormal bases; spontaneous deamination
RNA genomes have a problem with----
Cytosine deamination
Cytosine deamination produces -----; thus RNA genomes have-----
Uracil; high mutation rate
-----is important in Fragile X syndrome
CGG mUtation
DNA genomes have a problem with ------
Methyl-cytosine deamination
Human cells silence transcription by ---- at ----
Methylating cytosine; CGG sites
Due animation of methyl-C yields ----
Over evolutionary time, dream inaction has led to a paucity of ----in the----. Why hasn't it disappeared entirely
CGG; human genomes; methylation plays important role in regulating gene expression - if suddenly lose CpG individual would not be healthy
Why can't mismatch repair system fix deanimation
Because not linked to replication
-----find damaged bases
How do glycosylases fix damaged bases.? The glycosylases ----the _____out of the DNA, a-----in the protein binds to the ---- and glycosylases cleave ------ creating an ----site
Flips; base; pocket; base; glycosyl bonds;; AP site
What kind of base fits in a glycosylases binding site?what happens when a glycosylases stumbles upon a uracil?
Uracil; it cleaves it out of the sequence
Glycosylases are specific to the -----for which they are -----
Abnormal base; designed
BER removes ------ and repairs----
Damaged bases ; AP sites
AP sites created at high frequency because -----and----
1) there can be spontaneous loss of bases 2) uracil produced by spontaneous deanimation
Base excision repair lacks
When DNA backbone is missing a base, it is referred to as
An AP site
Base excision repair chooses ----over---- by using -----
Speed ; accuracy; pol beta
Each glycosylases recognizes ------
Specific abnormal base
----recruits ----to the breaks
PARP1; pol beta
-------binds to ------; ---- binding activates PARP1 to modify -----by using----to make ----; PARP1 activation recruits -------
PARP1; single strand DNA breaks; DNA binding; DNA proteins ( including itself); NAD, polymers of ADP-ribose; pol eta
Surprisingly, PARP1 KO mice are healthy! Why ?
Suppose single strand break in DNA sequence -if PARP1 doesn't do it's job the replication fork advances to convert a single strandbreak into a double strand break which can be fixed by homologous recombination -explains why mice can survive
In hereditary breast and ovarian cancer the is a higher risk for breast cancer due to defects in which genes?
BRCA 1/2
Normal cells with a mutation in ONE copy of BRCA1 survive because they still do -----; Tumors in whichbothalleles are mutated will ----
Homologous recombination; die
-----saves PARP1 deficient cells
Homologous recombination
Normal cells with a mutation in one copy of BRCA1 -----; but cancer cells with mutations in both copies of BRCA1----
-----kills BRCA1 mutant Tumors
Olaparib works by ---------; the ----of two disruptions produces ----; ----provides a back-up repair system for _____;Cancer cells survive disruption of one pathway, but die with the disruption of ____; ____ lethality spares the normal cells
Synthetic lethality, synthesis, lethality; homologous recombination; base excision repair; a second pathway; synthetic
Give three examples of the type of toxins Nucleotide Excision Repair Recognizes
benzo(a)pyrene (tobacco smoke); alfatoxin (aspergillus fungus); pyrimidine dimer (UV from the sun)
tobacco smoke
____ percent of all cancers are related to tobacco
___ from ___ causes hepatoma, the most common cancer world-wide
aflatoxin; aspergillus
___ is a fungus found in ___
aspergillus; grain
Ultraviolet radiation induces:
DNA nicks, cyclobutane thymine dimers, 6-4 pyrimidine dimers
Nucleotide excision repair excises an ____ spanning the ____
oligonucleotide; lesion
____ is the most carcinogenic compound ever created
_____, ___, and ____ form DNA adducts
Aflatoxin; benzo(a)pyrene; pyrimidine dimer
A ___ hardly produces any perturbation in the double helix because____
cyclobutane thymine dimer; bases are stacked
____ has DNA helicase activity
transcription factor IIH (TFIIH)
Nucleotide excision repair occurs by 2 overlapping pathways...Name them:
transcription coupled repair and global genomic repair
Transcription coupled repair _____ and ______ on ___
recognizes; removes lesions on the transcribed DNA strands
_______ recognizes and removes lesions on the transcribed DNA strands
transcription coupled repair
Global genomic repair ____ and ____
recognizes and repairs lesions throughout the genome
______ is repaired 2X faster than ____
Transcribed DNA; nontranscribed DNA
Inherited defects in Nucleotide Excision Repair causes _____
severe sun sensitivity
Name two diseases caused by defects in Nucleotide Excision Repair
Xeroderma pigmentosum; cockayne's syndrome
Xeroderma pigmentosum has _____inheritance
autosomal recessive
Xeroderma =
dry skin
abnormal pigmentation
Xeroderma pigmentosum is characterized by ____, _____, _____, ____ and ___
autosomal recessive inheritance; dry skin; abnormal pigmentation; sun sensitivity; severe risk for skin cancer
Xeroderma pigmentosum has ____ complementation groups
Each complementation group is ____ in a ____
defective ; specific gene
Xeroderma pigmentosum's complementation groups C and E are
defective in global genomic repair and less severe sun sensitivity
Xeroderma pigmentosum's complementation groups A, B, D, F, G are
defective in global genomic repair and transcription coupled repair; severe sun sensitivity ; mental retardation
Why does Xeroderma pigmentosum cause blistering?
Causes blistering because cells are dying very quickly; almost immediate cell death; all transcription stops right away
Cockayne's syndrome is a ____ in _____
defect; transcription coupled repair
Cockayne's syndrome is characterized by ____, ____, ____, ____, ____.
autosomal recessive inheritance, sun sensitivity, premature aging, cachectic dwarfism, and no risk for skin cancer
Why isn't Cockayne's syndrome characterized by the risk of skin cancer
Because global genomic repair suffices to prevent cancer
Mutations in telomerase cause ____, ____, and ____, alone or in combination
dyskeratosis congenita, aplastic anemia, pulmonary fibrosis
___ and ___ mutations cause pure CS
____ and ___ mutations cause mixed XP/CS
____ and ____ are the two subunits of TFIIH that have its helicase activities
XPB and XPD are the two subunits of ___ that have its ___
TFIIH ; helicase activities
XPS and XPD mutations can also cause _____
pure XP
The mystery of the XP variant: ____ are the same as XP (specify); ___ are different from XP (specify)
Clinical features (sun sensitivity and skin cancer); biochemical features (normal NER and pause of replication forks after UV exposure)
Mystery solved: XP variant is defective in ____
an error-prone polymerase (pol eta)
Loss of DNA pol eta is ____
____ is one of 7 ______ which perform ____
pol eta; 7 error-prone polymerases; trans-lesion synthesis
_____ defects explain XP variant symptoms: _____(many cells die when replication forks pause at the UV lesions) and _____(other error-prone polymerases create mutations)
Pol eta; sun sensitivity; skin cancer
___ ___ _ ___ create mutations that lead to cancer
Error prone polymerases
Name two mechanisms that prevent uncontrolled growth
Cell cycle regulation; telomere shortening
Carcinogenesis requires ___ or ___ ___
6 or 7 mutations
Four reasons why cancers are difficult to cure
1. multiple mechanisms to prevent uncontrolled growth; 2. cancer cells must inactivate several mechanisms 3. carcinogenesis requires 6 or 7 mutations 4. cancers develop resistance to treatment
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