Transcript student presentation 3

Nermeen Jouda
430203995
Bch 550
Supervised by Dr Gihan
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First, spontaneous reactions (mostly
hydrolysis)example: deamination.
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Second, our own metabolism generates
reactive oxygen and nitrogen species,
all of which damage DNA.
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Third, DNA is damaged by exogenous
physical and chemical agents.
DNA Lesion
Example/Cause
Missing base
Removal of purines by acid and heat (under physiological
conditions ≈104 purines/day/cell in a mammalian genome);
removal of altered bases (e.g., uracil) by DNA glycosylases
Altered base
Ionizing radiation; alkylating agents (e.g., ethylmethane sulfonate)
Incorrect base
Mutations affecting 3′ → 5′ exonuclease proofreading of incorrectly
incorporated bases
Bulge due to deletion
Intercalating agents (e.g., acridines) that cause addition or loss of
or insertion of a
a nucleotide during recombination or replication
nucleotide
Linked pyrimidines
Cyclotubyl dimers (usually thymine dimers) resulting from UV
irradiation
Singleor
double- Breakage of phosphodiester bonds by ionizing radiation or
chemical agents (e.g., bleomycin)
strand breaks
Cross-linked strands
Covalent linkage of two strands by bifunctional alkylating agents
(e.g., mitomycin C)
3′-deoxyribose
fragments
Disruption of deoxyribose structure by free radicals leading to
strand breaks

Nucleotide-excision repair eliminates helixdistorting lesions — such as those caused by
Uv induced photoproducts — in a multistep,
“cut and- patch” reaction that involves
more than 30 proteins .It has two branches:
 global genome repair, which probes the
genome for strand distortions

transcription-coupled repair, which
removes distorting lesions that block
elongating RNA polymerases

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Hypersensitivity to the sun
skin cancer.
defects in global repair,
with or without
deficiencies in
transcription- coupled
repair of distorting lesions.
accelerated
neurodegeneration
Defects in the repairenzyme genes XPA
through XPG.
UV sensitive .
 Growth failure.
 No skin cancer.
 Impaired sexual development
 severe and progressive neurodysfunction
 Mutations in transcriptioncoupled repair in the gene
encoding CSA or CSB combind
with XPB, XPD and XPG

 UV
sensetive
 Similar to Cockayne’s
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Syndrome in addition to
brittle (unfinished)
hair and nails
Point mutations in the genes
encoding XPB and XPD
Excision repair in cancer and aging.
 UV lesions and helix-distorting chemical adducts
are recognized and repaired by a multi-protein
nucleotide excision repair (NER) complex
comprising two pathways:

global genome (GG) NER and transcriptioncoupled excision repair (TCR).

Patients who have a defective GG-NER pathway
are highly susceptible to skin cancer, whereas
defects in TCR lead to progeroid syndromes.

DNA damage can trigger the development
of cancer, accelerate aging, or both,
depending on the type, amount, and
location of the damage.

When the damage is not repaired, the
outcome may be cancer or, if cell death or
senescence occurs, protection from
cancer, but the trade-off is acceleration of
the aging process.