Abstract
DNA-protein cross-links (DPC) are formed by a variety of radiations and chemicals which act via free radical formation. Covalency is inferred from the resistance of the cross-links to harsh treatments. In mammalian cells, a background of DPC (6000 per V79 cell) may result from normal associations of chromosomal loops with the nuclear protein matrix. After ionizing radiation, the elevated level of DPC (150 per Gy per V79 cell) are enriched in actively transcribing DNA and in a subset of proteins of the nuclear matrix. DPC formation is reduced by hydroxyl radical scavengers, by oxygen, and by hypertonic medium and is enhanced by hypotonic medium and by removal of intracellular glutathione. DPC are repaired more slowly than single-strand breaks and not at all when formed during metaphase. During the postirradiation period, changes in the sequence composition of the DNA of residual DPC are consistent with the preferential repair of DPC in actively expressed genes. Excision repair mechanisms have been proposed. Unrepaired DPC may block normal functions of the nuclear matrix, such as replication and transcription.
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- Banjar Z. M., Hnilica L. S., Briggs R. C., Stein J., Stein G. Crosslinking of chromosomal proteins to DNA in HeLa cells by UV gamma radiation and some antitumor drugs. Biochem Biophys Res Commun. 1983 Jul 29;114(2):767–773. doi: 10.1016/0006-291x(83)90847-1. [DOI] [PubMed] [Google Scholar]
- Biaglow J. E., Varnes M. E., Tuttle S. W., Oleinick N. L., Glazier K., Clark E. P., Epp E. R., Dethlefsen L. A. The effect of L-buthionine sulfoximine on the aerobic radiation response of A549 human lung carcinoma cells. Int J Radiat Oncol Biol Phys. 1986 Jul;12(7):1139–1142. doi: 10.1016/0360-3016(86)90244-0. [DOI] [PubMed] [Google Scholar]
- Chiu S. M., Friedman L. R., Sokany N. M., Xue L. Y., Oleinick N. L. Nuclear matrix proteins are crosslinked to transcriptionally active gene sequences by ionizing radiation. Radiat Res. 1986 Jul;107(1):24–38. [PubMed] [Google Scholar]
- Chiu S. M., Friedman L. R., Xue L. Y., Oleinick N. L. Modification of DNA damage in transcriptionally active vs. bulk chromatin. Int J Radiat Oncol Biol Phys. 1986 Aug;12(8):1529–1532. doi: 10.1016/0360-3016(86)90209-9. [DOI] [PubMed] [Google Scholar]
- Chiu S. M., Oleinick N. L., Friedman L. R., Stambrook P. J. Hypersensitivity of DNA in transcriptionally active chromatin to ionizing radiation. Biochim Biophys Acta. 1982 Oct 29;699(1):15–21. doi: 10.1016/0167-4781(82)90166-x. [DOI] [PubMed] [Google Scholar]
- Chiu S. M., Sokany N. M., Friedman L. R., Oleinick N. L. Differential processing of ultraviolet or ionizing radiation-induced DNA-protein cross-links in Chinese hamster cells. Int J Radiat Biol Relat Stud Phys Chem Med. 1984 Dec;46(6):681–690. doi: 10.1080/09553008414551921. [DOI] [PubMed] [Google Scholar]
- Cress A. E., Bowden G. T. Covalent DNA-protein crosslinking occurs after hyperthermia and radiation. Radiat Res. 1983 Sep;95(3):610–619. [PubMed] [Google Scholar]
- Fornace A. J., Jr Detection of DNA single-strand breaks produced during the repair of damage by DNA-protein cross-linking agents. Cancer Res. 1982 Jan;42(1):145–149. [PubMed] [Google Scholar]
- Fornace A. J., Jr, Little J. B. DNA crosslinking induced by x-rays and chemical agents. Biochim Biophys Acta. 1977 Aug 16;477(4):343–355. doi: 10.1016/0005-2787(77)90253-2. [DOI] [PubMed] [Google Scholar]
- Grunicke H., Bock K. W., Becher H., Gäng V., Schnierda J., Puschendorf B. Effect of alkylating antitumor agents on the binding of DNA to protein. Cancer Res. 1973 May;33(5):1048–1053. [PubMed] [Google Scholar]
- Hemminki K., Vainio H. Preferential binding of benzo[a]pyrene into nuclear matrix fraction. Cancer Lett. 1979 Mar;6(3):167–173. doi: 10.1016/s0304-3835(79)80028-2. [DOI] [PubMed] [Google Scholar]
- Mee L. K., Adelstein S. J. Predominance of core histones in formation of DNA--protein crosslinks in gamma-irradiated chromatin. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2194–2198. doi: 10.1073/pnas.78.4.2194. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mee L. K., Adelstein S. J. Radiolysis of chromatin extracted from cultured mammalian cells: formation of DNA-protein cross links. Int J Radiat Biol Relat Stud Phys Chem Med. 1979 Oct;36(4):359–366. doi: 10.1080/09553007914551141. [DOI] [PubMed] [Google Scholar]
- Meyn R. E., vanAnkeren S. C., Jenkins W. T. The induction of DNA-protein crosslinks in hypoxic cells and their possible contribution to cell lethality. Radiat Res. 1987 Mar;109(3):419–429. [PubMed] [Google Scholar]
- Miller K. G., Liu L. F., Englund P. T. A homogeneous type II DNA topoisomerase from HeLa cell nuclei. J Biol Chem. 1981 Sep 10;256(17):9334–9339. [PubMed] [Google Scholar]
- Minsky B. D., Braun A. X-ray-mediated cross linking of protein and DNA. Radiat Res. 1977 Sep;71(3):505–515. [PubMed] [Google Scholar]
- Mullenders L. H., van Zeeland A. A., Natarajan A. T. Comparison of DNA loop size and super-coiled domain size in human cells. Mutat Res. 1983 Aug;112(4):245–252. doi: 10.1016/0167-8817(83)90010-x. [DOI] [PubMed] [Google Scholar]
- Nelson E. M., Tewey K. M., Liu L. F. Mechanism of antitumor drug action: poisoning of mammalian DNA topoisomerase II on DNA by 4'-(9-acridinylamino)-methanesulfon-m-anisidide. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1361–1365. doi: 10.1073/pnas.81.5.1361. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Niggli H. J., Cerutti P. A. Nucleosomal distribution of thymine photodimers following far- and near-ultraviolet irradiation. Biochem Biophys Res Commun. 1982 Apr 14;105(3):1215–1223. doi: 10.1016/0006-291x(82)91098-1. [DOI] [PubMed] [Google Scholar]
- Oleinick N. L., Chiu S. M., Friedman L. R. Gamma radiation as a probe of chromatin structure: damage to and repair of active chromatin in the metaphase chromosome. Radiat Res. 1984 Jun;98(3):629–641. [PubMed] [Google Scholar]
- Olinski R., Briggs R. C., Hnilica L. S. Gamma-radiation-induced crosslinking of cell-specific chromosomal nonhistone protein-DNA complexes in HeLa chromatin. Radiat Res. 1981 Apr;86(1):102–114. [PubMed] [Google Scholar]
- Peak J. G., Peak M. J., Sikorski R. S., Jones C. A. Induction of DNA-protein crosslinks in human cells by ultraviolet and visible radiations: action spectrum. Photochem Photobiol. 1985 Mar;41(3):295–302. doi: 10.1111/j.1751-1097.1985.tb03488.x. [DOI] [PubMed] [Google Scholar]
- Ramakrishnan N., Chiu S. M., Oteinick N. L. Yield of DNA-protein cross-links in gamma-irradiated Chinese hamster cells. Cancer Res. 1987 Apr 15;47(8):2032–2035. [PubMed] [Google Scholar]
- Rayshell M., Ross J., Werbin H. Evidence that N-acetoxy-N-acetyl-2-aminofluorene crosslinks DNA to protein by a free radical mechanism. Carcinogenesis. 1983;4(5):501–507. doi: 10.1093/carcin/4.5.501. [DOI] [PubMed] [Google Scholar]
- Smith K. C. A mixed photoproduct of thymine and cysteine: 5-S-cysteine, 6-hydrothymine. Biochem Biophys Res Commun. 1970;39(6):1011–1016. doi: 10.1016/0006-291x(70)90658-3. [DOI] [PubMed] [Google Scholar]
- Strniste G. F., Rall S. C. Induction of stable protein-deoxyribonucleic acid adducts in Chinese hamster cell chromatin by ultraviolet light. Biochemistry. 1976 Apr 20;15(8):1712–1719. doi: 10.1021/bi00653a019. [DOI] [PubMed] [Google Scholar]
- Wedrychowski A., Ward W. S., Schmidt W. N., Hnilica L. S. Chromium-induced cross-linking of nuclear proteins and DNA. J Biol Chem. 1985 Jun 10;260(11):7150–7155. [PubMed] [Google Scholar]
- Williams J. I., Friedberg E. C. Deoxyribonucleic acid excision repair in chromatin after ultraviolet irradiation of human fibroblasts in culture. Biochemistry. 1979 Sep 4;18(18):3965–3972. doi: 10.1021/bi00585a019. [DOI] [PubMed] [Google Scholar]