Defective Repair Replication of DNA in Xeroderma Pigmentosum

@article{Cleaver1968DefectiveRR,
  title={Defective Repair Replication of DNA in Xeroderma Pigmentosum},
  author={James E. Cleaver},
  journal={Nature},
  year={1968},
  volume={218},
  pages={652-656}
}
Normal skin fibroblasts can repair ultraviolet radiation damage to DNA by inserting new bases into DNA in the form of small patches. Cells from patients with the hereditary disease xeroderma pigmentosum carry a mutation such that repair replication of DNA is either absent or much reduced in comparison to normal fibroblasts. Patients with xeroderma pigmentosum develop fatal skin cancers when exposed to sunlight, and so the failure of DNA repair in the skin must be related to carcinogenesis. 
DNA repair and radiation sensitivity in human (xeroderma pigmentosum) cells.
  • J. Cleaver
  • Biology, Medicine
  • International journal of radiation biology and related studies in physics, chemistry, and medicine
  • 1970
TLDR
The results demonstrate the importance of repair replication in the survival of irradiated mammalian cells and in the aetiology of xeroderma pigmentosum. Expand
Relationship of DNA repair to carcinogenesis in xeroderma pigmentosum.
TLDR
Radioautograms of intact ultraviolet (UV)-irradiated epidermis from a patient with xeroderma pigmentosum showed no detectable abnormality in UV-induced thymidine- 3 H incorporation, suggesting that some mechanism other than enhancement of UV carcinogenesis by defective DNA repair may be responsible for skin tumor formation in this patient. Expand
Repair of DNA damaged by alkylating carcinogens is defective in xeroderma pigmentosum-derived fibroblasts
TLDR
Direct measurement of the amounts of two products formed by alkylating carcinogens in the DNA and of the rate at which they are eliminated indicates that XP cells have a defect in this type of repair also. Expand
Genetic heterogeneity of xeroderma pigmentosum demonstrated by somatic cell hybridization.
TLDR
Using the dark repair mechanism in microorganisms as a model, evidence has been presented that XP cells are defective in the incision step of DNA repair3–5. Expand
Complementation of the xeroderma pigmentosum DNA repair defect in cell-free extracts
Soluble extracts from human lymphoid cell lines that perform repair synthesis on covalently closed circular DNA containing pyrimidine dimers or psoralen adducts are described. Short patches ofExpand
Defect in DNA Synthesis in Skin of Patients with Xeroderma Pigmentosum Demonstrated in vivo
Exposure of normal human skin in vivo to ultraviolet irradiation at wavelengths shorter than 320 nanometers stimtulated an unscheduled DNA synthesis in all of the cell layers of the epidermis and inExpand
Repair of DNA in xeroderma pigmentosum conjunctiva.
TLDR
Cells from most XP patients are deficient in repairing DNA damaged by ultraviolet (UV) light as shown by a reduced rate of tritiated thymidine (3HTdR) incorporation during their DNA repair synthesis. Expand
Defective DNA Repair in Cultured Melanocytes from Xeroderma Pigmentosum Patients
The DNA repair of ultraviolet (UV)‐induced damages in primary cultured melanocytes from xeroderma pigmentosum (XP) patients and normal subjects were studied by measuring unscheduled DNA synthesisExpand
Historical aspects of xeroderma pigmentosum and nucleotide excision repair.
  • J. Cleaver
  • Biology, Medicine
  • Advances in experimental medicine and biology
  • 2008
TLDR
The discovery that xeroderma pigmentosum was a sun-sensitive hereditary human disease that was deficient in DNA repair was made when research into the fundamental mechanisms of nucleotide excision repair was in its infancy and established DNA repair as a central factor for maintaining genomic stability and preventing cancer, neurodegenerative disease and aging. Expand
Genetic Analysis of DNA Repair Defect in Xeroderma Pigmentosum Cells: Identification of Complementing Genes
TLDR
Very little is known about the details of biochemical events involved in repair of DNA damage in human cells, but genes involved in several of the various repair pathways have been cloned. Expand
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