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Biochem Ch. 35.1-35.3
Biochem Ch. 35.1-35.3
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Biochemistry
Undergraduate 3
04/02/2018

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Term
the simplest source of damage in the DNA double helix
Definition
errors introduced in the replication process
Term
how mismatching DNA bases causes damage
Definition
distorts double helix, which can become mutagenic
Term
how a mismatch of bases is mutagenic
Definition
results in daughter helices with different sequences
Term
some types of errors in DNA
Definition
-mismatches
-insertions
-deletions
-breaks in one or both strands
Term
how errors in DNA can inhibit replication
Definition
replicative polymerases can stall or fall off the damaged template entirely, making replication of the genome halt before it's complete
Term
one way to repair damage in DNA
Definition
translesion or error-prone polymerases
Term
function of translesion or error-prone polymerases
Definition
allow for the completion of a draft sequence of the damaged area of the genome that can be at least partly repaired by DNA-repair processes
Term
drawback to the use of translesion or error-prone polymerases
Definition
substantially more error prone than other polymerases when replicating DNA
Term
depiction of triplet-repeat expansion
Definition
refer to p. 644
Term
bases in DNA can be damaged by...
Definition
-oxidizing agents
-alkylating agents
-light
Term
mutagens
Definition
chemical agents that alter specific bases within DNA after replication is complete
Term
how hydroxyl radical (a reactive oxygen species) is mutagenic
Definition
converts guanine to 8-oxoguanine, which is mutagenic because it pairs with adenine instead of cytosine
Term
depiction of guanine oxidation
Definition
refer to p. 645

this is mutagenic
Term
how deamination causes mutations
Definition
example: deaminates adenine to form hypoxanthine, which pairs with cytosine instead of thymine
Term
depiction of adenine deamination
Definition
refer to p. 645

this causes mutations
Term
example of alkylation
Definition
aflatoxin B1, which is produced by molds that grow on peanuts and other foods
Term
how aflatoxin B1 causes mutations
Definition
cytochrome P450 enzyme converts it into a highly reactive epoxide, which reacts with the N-7 atom of guanine to form a mutagenic adduct that binds with adenine instead of cystine
Term
depiction of aflatoxin B1 activation
Definition
refer to p. 646

causes mutations
Term
the most pertvasive DNA-damaging agent
Definition
the UV light from sunlight
Term
how UV light damages DNA
Definition
by covalently linking adjacent pyrimidine residues along the DNA strand
Term
depiction of a cross-linked dimer of 2 thymine bases
Definition
refer to p. 647
Term
how high energy em radiation, such as X-rays, damages DNA
Definition
by producing high concentrations of reactive chemicals

also causes sinbgle- and double-stranded breaks
Term
many systems repair DNA by...
Definition
using sequence information from the uncompromised strand
Term
mechanistic outline followed by many single-strand replication systems
Definition
1: recognize the offending base(s)
2: remove the offending base(s)
3: repair the resulting gap with a DNA polymerase ad a DNA ligase
Term
a mechanism in essentially all cells that corrects errors not corrected by proofreading
Definition
mismatch repair
Term
how mismatch repair works in E. coli
Definition
1: detecting mismatch
2: removing part of the strand containing the mismatch
3: replace it with correct sequence
Term
the mismatch repair proteins in E. coli
Definition
-MutS
-MutL
Term
the endonuclease in E. coli
Definition
MutH
Term
depiction of mismatch repair
Definition
refer to p. 647
Term
how mismatch repair machinery determines incorrect base in E. coli
Definition
some adenine bases in the parent strand are methylated, whereas the newly synthesized daughter strand is not yet methylated. thus, the machinery recognizes that the methylated base is correct and the unmethylated mismatch is incorrect
Term
direct repair
Definition
repairing damage to DNA without having to remove any fragments of the DNA
Term
DNA photolyase
Definition
a photoreactivating enzyme that direct repairs DNA by photochemical cleavage of pyrimidine dimers
Term
how photochemical cleavage works
Definition
photolytic enzyme binds to distorted region and absorbs photon to form an excited state that cleaves the dimer into its component bases
Term
what happens to damaged bases in E. coli?
Definition
excised by enzym AlkylA
Term
base-excision repair
Definition
replacing damaged bases with undamaged bases
Term
depiction of base-excision repair
Definition
refer to p. 648
Term
DNA glycosylase
Definition
removes damaged base
Term
AP site
Definition
site in DNA strand devoid of base
Term
AP endonuclease
Definition
knicks the backbone adjacent to the missing base
Term
deoxyribose phosphodiesterase
Definition
excites residual phosphate unit
Term
role of DNA polymerase I in base-excision repair
Definition
inserts undamaged nucleotide
Term
how the base-excision-repair system know to remove T in the T-G pair
Definition
because the C-->T mutation is so common
Term
depiction of the deamination of 5-methylcytosine forms thymine.
Definition
refer to p. 648
Term
what mechanism recognizes improper nucleotide pairs that escape the base-excision-repair system?
Definition
nucleotide-excision repair
Term
what the nucleotide-excision repair system does
Definition
recognizes distortions in the DNA double-helix caused by the presence of a damaged base
Term
depiction of nucleotide-excision repair
Definition
refer to p. 649
Term
excinuclease
Definition
in nucleotide-excision repair, this cuts out DNA sequence that contains the defective base
Term
why DNA uses thymine instead of uracil
Definition
-cytosine spontaneously deaminates to form uracil
-thymine contains methyl group, but uravil instead contains an H in that place
-thus, the methyl group is a tag that distinguishes thymine from deaminated cytosine, which is uracil; this mechanism enhances the fidelity of the genetic message
Term
depiction of uracil repair
Definition
refer to p. 649
Term
uracil DNA glycosylase
Definition
hydrolyzes the glycosidic bond between the uracil and deoxyribose moieties, but does not attack thymine-containing nucleotides
Term
double-strand breaks arise when...
Definition
replication stalls
Term
one thing that can cause replication to stall
Definition
when the polymerase encounters an unrepaired nick in one of the template strands at the replication fork
Term
depiction of generation of a double-strand break
Definition
refer to p. 651
Term
things that can cause double-strand breaks
Definition
-unrepaired nicks
-ionizing radiation, such as gamma rays and X-rays
Term
what happens when the replication machinery encounters a nick in the DNA?
Definition
the replication fork collapses, leaving a double-stranded break on one of the daughter helices
Term
types of ionizing radiation that can cause double-stranded breaks
Definition
-x-rays
-gamma rays

they are powerful enough to break the DNA backbone
Term
where recombination is most efficient
Definition
between stretches of DNA that are similar in sequence
Term
homologous recombination
Definition
parent DNA duplexes align at regions of sequence similarity, and new DNA molecules are formed by the breaking and joining of homologous segments
Term
one key protein in recombination in humans
Definition
RAD 51, which is an ATPase that binds single-stranded DNA
Term
depiction of repair of double-strand break by using recombination
Definition
refer to p. 652
Term
something recombination between alleles can be used for
Definition
generation of new DNA sequences and molecular diversity
Term
a biochemical tool recombination is the foundation for
Definition
-gene knock-out
-gene knock-in
Term
gene knock-out
Definition
specific gene is deleted
Term
gene knock-in
Definition
specific gene is inserted
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