DNA Single-strand Breaks During Repair of UV Damage in Human Fibroblasts and Abnormalities of Repair in Xeroderma Pigmentosum

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1976 Jan 1

PMID 1751

Citations 27

Authors

A J Fornace Jr

K W Kohn

H E KANN Jr

Affiliations

Soon will be listed here.

Abstract

The method of DNA alkaline elution was applied to a study of the formation and resealing of DNA single-strand breaks after irradiation of human fibroblasts with ultraviolet light (UV). The general features of the results were consistent with current concepts of DNA excision repair, in that breaks appeared rapidly after UV, and resealed slowly in normal fibroblasts, whereas breaks did not appear in those cells of patients with xeroderma pigmentosum (XP) that are known to have defects in DNA repair synthesis. The appearance of breaks required a short post-UV incubation, consistent with the expected action of an endonuclease. Cells of the variant form of XP characterized by normal DNA repair synthesis exhibited normal production of breaks after UV, but were slower than normal cells in resealing these breaks. This difference was enhanced by caffeine. A model is proposed to relate this finding with a previously described defect in post-replication repair in these XP variant cells. DNA crosslinking appears to cause an underestimate in the measurement of DNA breakage after UV.

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References

Lehmann A, Arlett C, Paterson M, Lohman P, BOOTSMA D . Xeroderma pigmentosum cells with normal levels of excision repair have a defect in DNA synthesis after UV-irradiation. Proc Natl Acad Sci U S A. 1975; 72(1):219-23. PMC: 432274. DOI: 10.1073/pnas.72.1.219. View

Uhlenhopp E, ZIMM B . Viscoelastic characterization of single-stranded DNA from Escherichia coli. Biophys J. 1975; 15(3):223-32. PMC: 1334619. DOI: 10.1016/S0006-3495(75)85813-9. View

Day R . Xeroderma pigmentosum variants have decreased repair of ultraviolet-damaged DNA. Nature. 1975; 253(5494):748-9. DOI: 10.1038/253748a0. View

Smith K . Dose dependent decrease in extractability of DNA from bacteria following irradiation with ultraviolet light or with visible light plus dye. Biochem Biophys Res Commun. 1962; 8:157-63. DOI: 10.1016/0006-291x(62)90255-3. View

Rydberg B . The rate of strand separation in alkali of DNA of irradiated mammalian cells. Radiat Res. 1975; 61(2):274-87. View

Regan J, Setlow R . Two forms of repair in the DNA of human cells damaged by chemical carcinogens and mutagens. Cancer Res. 1974; 34(12):3318-25. View

Kohn K, Friedman C, Ewig R, Iqbal Z . DNA chain growth during replication of asynchronous L1210 cells. Alkaline elution of large DNA segments from cells lysed on filters. Biochemistry. 1974; 13(20):4134-9. DOI: 10.1021/bi00717a011. View

Buhl S, Setlow R, Regan J . Steps in DNA chain elongation and joining after ultra-violet irradiation of human cells. Int J Radiat Biol Relat Stud Phys Chem Med. 1972; 22(5):417-24. DOI: 10.1080/09553007214551301. View

AHNSTROM G, Erixon K . Radiation induced strand breakage in DNA from mammalian cells. Strand separation in alkaline solution. Int J Radiat Biol Relat Stud Phys Chem Med. 1973; 23(3):285-9. DOI: 10.1080/09553007314550311. View

10.

Jolley G, Ormerod M . An improved method for measuring cross-links in the DNA of mammalian cells: the effect of nitrogen mustard. Biochim Biophys Acta. 1973; 308(2):242-51. DOI: 10.1016/0005-2787(73)90154-8. View

11.

ROBBINS J, Kraemer K, LUTZNER M, Festoff B, Coon H . Xeroderma pigmentosum. An inherited diseases with sun sensitivity, multiple cutaneous neoplasms, and abnormal DNA repair. Ann Intern Med. 1974; 80(2):221-48. DOI: 10.7326/0003-4819-80-2-221. View

12.

SIMUKOVA N, BUDOWSKY E . Conversion of non-covalent interactions in nucleoproteins into covalent bonds: UV-induced formation of polynucleotide-protein crosslinks in bacteriophage Sd virions. FEBS Lett. 1974; 38(3):299-303. DOI: 10.1016/0014-5793(74)80077-3. View

13.

GLISIN V, Doty P . The cross-linking of DNA by ultraviolet radiation. Biochim Biophys Acta. 1967; 142(2):314-22. DOI: 10.1016/0005-2787(67)90614-4. View

14.

Kohn K, Spears C, Doty P . Inter-strand crosslinking of DNA by nitrogen mustard. J Mol Biol. 1966; 19(2):266-88. DOI: 10.1016/s0022-2836(66)80004-9. View

15.

Cleaver J . Xeroderma pigmentosum: variants with normal DNA repair and normal sensitivity to ultraviolet light. J Invest Dermatol. 1972; 58(3):124-8. DOI: 10.1111/1523-1747.ep12538913. View

16.

Ormerod M, Stevens U . The rejoining of x-ray-induced strand breaks in the DNA of a murine lymphoma cell (L5178Y). Biochim Biophys Acta. 1971; 232(1):72-82. DOI: 10.1016/0005-2787(71)90492-8. View

17.

Regan J, Setlow R, Ley R . Normal and defective repair of damaged DNA in human cells: a sensitive assay utilizing the photolysis of bromodeoxyuridine. Proc Natl Acad Sci U S A. 1971; 68(4):708-12. PMC: 389025. DOI: 10.1073/pnas.68.4.708. View

18.

Habazin V, Han A . Ultra-violet-light-induced DNA-to-protein cross-linking in HeLa cells. Int J Radiat Biol Relat Stud Phys Chem Med. 1970; 17(6):569-75. DOI: 10.1080/09553007014550711. View

19.

Smith K . A mixed photoproduct of thymine and cysteine: 5-S-cysteine, 6-hydrothymine. Biochem Biophys Res Commun. 1970; 39(6):1011-6. DOI: 10.1016/0006-291x(70)90658-3. View

20.

BURK P, LUTZNER M, Clarke D, ROBBINS J . Ultraviolet-stimulated thymidine incorporation in xeroderma pigmentosum lymphocytes. J Lab Clin Med. 1971; 77(5):759-67. View