Xeroderma Pigmentosum (XPF)
description
Transcript of Xeroderma Pigmentosum (XPF)
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Xeroderma Pigmentosum (XPF)
Cara Mitchell
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Characteristics of XP
Extreme photosensitivity Early onset of skin cancers Blistering of skin from sun exposure Redness and inflammation of skin Discoloration, scarring, freckling Some neurological damage
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Affected Individual
http://www.inrp.fr/Acces/biotic/gpe/dossiers/xeroderma/html/phenomacr.htm
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Cause of XP
Mutation in one of the proteins involved in NER
Inability to repair UV damaged DNA Buildup of mutations in skin cells Increased incidence of skin cancers
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What is NER?
Nucleotide Excision Repair
Mechanism of DNA repair
Used in repairing UV damage
http://murray.francis.com/repair/3-UVcancer.htm
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NER in the cell
http://egp.gs.washington.edu/ner.html
Damage Recognition
Binding of protein complex
3’
Incision of DNA
5’
Oligonucleotide excision
DNA repair synthesis
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Complementation Groups
7 main proteins involved in NER Mutations are generally recessive Mutations in XPA-G are
complementary Different phenotypes possible
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XP-F
Milder phenotype Later onset of cancers Usually no neurological damage Lessened photosensitivity
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XPF Protein
Functions with ERCC1 protein XPF-ERCC1: endonuclease activity Incises DNA 5’ to the damage Mutations mostly in C-terminal half This half associates w/ ERCC1 and
has nuclease function
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Mouse Knockouts (XPF Deficient)
Severely defective postnatal growth Death at ~3 weeks Abnormal cells (esp. in liver) Embryonic fibroblasts hypersensitive to
UV and MMC
http://mcb.asm.org/cgi/content/full/24/3/1200
Liver Cells
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Back to the Big Picture
XPF: endonuclease activity in NER NER repairs UV damage to DNA Dysfunctional NER
Buildup of mutations
Cancer
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Protein Therapy
Now in clinical trials Introduces desired protein into cells Uses viral proteins Goes on via skin lotion! Does not help neurological problems
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Sources
Friedberg, Errol C. “How nucleotide excision repair protects against cancer”, Nature. Oct. 2001 vol. 1. Macmillan Magazines Ltd.
http://hmg.oupjournals.org/cgi/content/full/7/6/969
http://www.rarediseases.org/search/rdbdetail_abstract.html?disname=Xeroderma%20Pigmentosum
http://www.xps.org/ http://www.bio.unc.edu/courses/Biology99/
examples/Kramer.ppt#1 http://www.cse.ucsc.edu/research/compbio/DNA-
repair/euk-nucleotide-excision.html http://mcb.asm.org/cgi/content/full/24/3/1200
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Thanks for Listening!
Questions?