1. Nermeen Jouda 430203995 Bch 550 Supervised by Dr Gihan

4.  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.

6.  Nucleotide-excision repair eliminates helix- distorting 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

9.  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 repair- enzyme genes XPA through XPG.

10.  UV sensitive.  Growth failure.  No skin cancer.  Impaired sexual development  severe and progressive neuro- dysfunction  Mutations in transcription- coupled repair in the gene encoding CSA or CSB combind with XPB, XPD and XPG

11.  UV sensetive  Similar to Cockayne’s Syndrome in addition to brittle (unfinished)  hair and nails  Point mutations in the genes encoding XPB and XPD

12. 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 transcription- coupled 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.

14.  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.