Defective Repair Replication of DNA in Xeroderma Pigmentosum

  title={Defective Repair Replication of DNA in Xeroderma Pigmentosum},
  author={James E. Cleaver},
  • J. Cleaver
  • Published 18 May 1968
  • Biology, Medicine
  • Nature
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
  • Medicine, Biology
    International journal of radiation biology and related studies in physics, chemistry, and medicine
  • 1970
The results demonstrate the importance of repair replication in the survival of irradiated mammalian cells and in the aetiology of xeroderma pigmentosum.

Relationship of DNA repair to carcinogenesis in xeroderma pigmentosum.

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.

Repair of DNA damaged by alkylating carcinogens is defective in xeroderma pigmentosum-derived fibroblasts

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.

Genetic heterogeneity of xeroderma pigmentosum demonstrated by somatic cell hybridization.

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.

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 in

Repair of DNA in xeroderma pigmentosum conjunctiva.

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.

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 synthesis

Historical aspects of xeroderma pigmentosum and nucleotide excision repair.

  • J. Cleaver
  • Biology
    Advances in experimental medicine and biology
  • 2008
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.

Genetic Analysis of DNA Repair Defect in Xeroderma Pigmentosum Cells: Identification of Complementing Genes

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.



Repair of Damaged DNA in a Eucaryotic Cell: Tetrahymena pyriformis

An improved method for detecting repair synthesis is described and damage induced by ultraviolet light or x-rays to the DNA of a eucaryotic organism is repaired by a process similar to the repair system present in bacteria.


It has been demonstrated that substitution of thymidine by 5-bromodeoxyuridine or 5-iodode Oxyuridine greatly enhances the UV-sensitivity in the induction of mammalian chromosome breaks, suggesting that DNA is the primary target of the UV injury that leads to chromosome aberrations.

DNA repair and genetic recombination: studies on mutants of Escherichia coli defective in these processes.

Experiments on the mechanisms of DNA repair in Escherichia coli following exposure to irradiation or to mutagens, including alkylating agents and X-rays are reviewed and the role of DNA Repair in genetic recombination is reviewed.

Repair Replication in HeLa Cells after Large Doses of X-irradiation

It is reported that, after very large doses of X-rays to HeLa cells, incorporation of precursors into DNA occurs as a result of a process which has the characteristics of “repair-replication”, a phenomenon which has been correlated with enhanced survival in bacteria2.

Organization of the Deoxyribonucleic Acid Replicating System in Mammalian Cells as Revealed by the Use of X-Radiation and Bromuracil Deoxyriboside

Results are reported from studies of the effects of x radiation on the synthesis of desoxyribonucleic acid in HeLa and hamster cells in tissue culture and the concept of a very-high molecular weight DNA is discussed in relation to the data obtained.


The findings suggest that the enzymatic removal of injured bases, including thymine dimers, and the reconstruction of the DNA from information on the complementary strand may be an important biological mechanism for the preservation of DNA.


  • R. SetlowW. Carrier
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1964
The onset of DNA synthesis is associated with thymine dimer removal, which is suggested to be one step in cell recovery in resistant strains of E. coli.

The relationship between the rate of DNA synthesis and its inhibition by ultraviolet light in mammalian cells.

The observations were interpreted in terms of a model in which blocks to replication are introduced into DNA by irradiation and replication ceases when the first block is reached, which indicates that pyrimidine dimers may not be effective blocks in mammalian cells.