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Transcript student presentation 3

Nermeen Jouda
Bch 550
Supervised by Dr Gihan
First, spontaneous reactions (mostly
hydrolysis)example: deamination.
Second, our own metabolism generates
reactive oxygen and nitrogen species,
all of which damage DNA.
Third, DNA is damaged by exogenous
physical and chemical agents.
DNA Lesion
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
Linked pyrimidines
Cyclotubyl dimers (usually thymine dimers) resulting from UV
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)
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
Hypersensitivity to the sun
skin cancer.
defects in global repair,
with or without
deficiencies in
transcription- coupled
repair of distorting lesions.
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
 Similar to Cockayne’s
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.