Abstract
By using electromobility shift assay (EMSA), we have identified a protein able to recognize the DNA only if it was previously reacted with minor groove binders. This protein binds with very high affinity AT containing DNA treated with minor groove binders such as distamycin A, Hoechst 33258 and 33342, CC-1065 and ethidium bromide minor groove intercalator, but not with major groove binders such as quinacrine mustard, cisplatin or melphalan, or with topoisomerase I inhibitor camptothecin or topoisomerase II inhibitor doxorubicin. This protein was found to be present in different extracts of human, murine and hamster cells, with the human protein which appears to have a molecular weight slightly lower than that of the other species. This protein was found to be expressed both in cancer and normal tissues. By using molecular ultrafiltration techniques as well as southwestern analysis it was estimated that the apparent molecular weight is close to 100 kDa. We can exclude an identity between this protein and other proteins, with a similar molecular weight previously reported to be involved in DNA damage recognition/repair, such as topoisomerase I, mismatch repair activities such as the prokaryotic MutS protein and its human homologue hMSH2 or proteins of the nucleotide excision repair system such as ERCC1, -2, -3 and -4.
Full Text
The Full Text of this article is available as a PDF (144.8 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Arcamone F. M., Animati F., Barbieri B., Configliacchi E., D'Alessio R., Geroni C., Giuliani F. C., Lazzari E., Menozzi M., Mongelli N. Synthesis, DNA-binding properties, and antitumor activity of novel distamycin derivatives. J Med Chem. 1989 Apr;32(4):774–778. doi: 10.1021/jm00124a008. [DOI] [PubMed] [Google Scholar]
- Bellorini M., Moncollin V., D'Incalci M., Mongelli N., Mantovani R. Distamycin A and tallimustine inhibit TBP binding and basal in vitro transcription. Nucleic Acids Res. 1995 May 25;23(10):1657–1663. doi: 10.1093/nar/23.10.1657. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Broggini M., Coley H. M., Mongelli N., Pesenti E., Wyatt M. D., Hartley J. A., D'Incalci M. DNA sequence-specific adenine alkylation by the novel antitumor drug tallimustine (FCE 24517), a benzoyl nitrogen mustard derivative of distamycin. Nucleic Acids Res. 1995 Jan 11;23(1):81–87. doi: 10.1093/nar/23.1.81. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Broggini M., Ponti M., Ottolenghi S., D'Incalci M., Mongelli N., Mantovani R. Distamycins inhibit the binding of OTF-1 and NFE-1 transfactors to their conserved DNA elements. Nucleic Acids Res. 1989 Feb 11;17(3):1051–1059. doi: 10.1093/nar/17.3.1051. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chu G., Chang E. Xeroderma pigmentosum group E cells lack a nuclear factor that binds to damaged DNA. Science. 1988 Oct 28;242(4878):564–567. doi: 10.1126/science.3175673. [DOI] [PubMed] [Google Scholar]
- Cleaver J. E. It was a very good year for DNA repair. Cell. 1994 Jan 14;76(1):1–4. doi: 10.1016/0092-8674(94)90165-1. [DOI] [PubMed] [Google Scholar]
- Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hoeijmakers J. H. Nucleotide excision repair. II: From yeast to mammals. Trends Genet. 1993 Jun;9(6):211–217. doi: 10.1016/0168-9525(93)90121-w. [DOI] [PubMed] [Google Scholar]
- Hurley L. H., Reynolds V. L., Swenson D. H., Petzold G. L., Scahill T. A. Reaction of the antitumor antibiotic CC-1065 with DNA: structure of a DNA adduct with DNA sequence specificity. Science. 1984 Nov 16;226(4676):843–844. doi: 10.1126/science.6494915. [DOI] [PubMed] [Google Scholar]
- Imperatori L., Damia G., Taverna P., Garattini E., Citti L., Boldrini L., D'Incalci M. 3T3 NIH murine fibroblasts and B78 murine melanoma cells expressing the Escherichia coli N3-methyladenine-DNA glycosylase I do not become resistant to alkylating agents. Carcinogenesis. 1994 Mar;15(3):533–537. doi: 10.1093/carcin/15.3.533. [DOI] [PubMed] [Google Scholar]
- Li L. H., Swenson D. H., Schpok S. L., Kuentzel S. L., Dayton B. D., Krueger W. C. CC-1065 (NSC 298223), a novel antitumor agent that interacts strongly with double-stranded DNA. Cancer Res. 1982 Mar;42(3):999–1004. [PubMed] [Google Scholar]
- Mattes W. B., Lee C. S., Laval J., O'Connor T. R. Excision of DNA adducts of nitrogen mustards by bacterial and mammalian 3-methyladenine-DNA glycosylases. Carcinogenesis. 1996 Apr;17(4):643–648. doi: 10.1093/carcin/17.4.643. [DOI] [PubMed] [Google Scholar]
- Merino A., Madden K. R., Lane W. S., Champoux J. J., Reinberg D. DNA topoisomerase I is involved in both repression and activation of transcription. Nature. 1993 Sep 16;365(6443):227–232. doi: 10.1038/365227a0. [DOI] [PubMed] [Google Scholar]
- Pezzoni G., Grandi M., Biasoli G., Capolongo L., Ballinari D., Giuliani F. C., Barbieri B., Pastori A., Pesenti E., Mongelli N. Biological profile of FCE 24517, a novel benzoyl mustard analogue of distamycin A. Br J Cancer. 1991 Dec;64(6):1047–1050. doi: 10.1038/bjc.1991.463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reynolds V. L., Molineux I. J., Kaplan D. J., Swenson D. H., Hurley L. H. Reaction of the antitumor antibiotic CC-1065 with DNA. Location of the site of thermally induced strand breakage and analysis of DNA sequence specificity. Biochemistry. 1985 Oct 22;24(22):6228–6237. doi: 10.1021/bi00343a029. [DOI] [PubMed] [Google Scholar]
- Seeberg E., Eide L., Bjørås M. The base excision repair pathway. Trends Biochem Sci. 1995 Oct;20(10):391–397. doi: 10.1016/s0968-0004(00)89086-6. [DOI] [PubMed] [Google Scholar]
- Yeh Y. C., Liu H. F., Ellis C. A., Lu A. L. Mammalian topoisomerase I has base mismatch nicking activity. J Biol Chem. 1994 Jun 3;269(22):15498–15504. [PubMed] [Google Scholar]