Abstract
The HMG domain is a recently discovered motif which occurs in transcription factors and other DNA-binding proteins. The domain, composed of approximately 80 amino acids, was first identified in the abundant nonhistone chromosomal protein HMG1, high mobility group protein 1, so named because of its rapid mobility on Polyacrylamide electrophoresis gels. Some HMG-domain proteins, such as LEF-1 and SRY, contain a single HMG domain, whereas others, including hUBF, have up to five. In binding to DNA, the HMG domain prefers single-stranded or bent double-stranded structures. Proteins containing the domain bend duplex DNA by up to 130° when they bind to it, and HMG1 facilitates the formation of DNA circles as small as 59 bp in length. HMG-domain proteins also bind to the most abundant DNA adducts of the anticancer drug cisplatin, specifically, the 1,2-d(GpG) and 1,2-d(ApG) intrastrand cross-links. These adducts are believed to be responsible for the cytotoxicity of the drug. HMG-domain proteins may affect the antitumor properties of cisplatin, since they block excision repair of the cisplatin-DNA adducts both in human cell extracts and in yeast cells.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Bellon SF, Lippard SJ (1990) Bending studies of DNA site-specifically modified by cisplatin, trans-diamminedichloroplatinum(II) and cis-[Pt(NH3)2(N3-cytosine)Cl]+. Biophys Chem 35:179–188
Bellon SF, Coleman JH, Lippard SJ (1991) DNA unwinding produced by sitespecific intrastrand cross-links of the antitumor drug cis-diamminedichloroplatinum (II). Biochemistry 30:8026–8035
Billings PC, Davis RJ, Engelsberg BN, Skov KA, Hughes EN (1992) Characterization of high mobility group protein binding to cisplatin-damaged DNA. Biochem Biophys Res Comm 188:1286–1294
Bissett D, McLaughlin K, Kelland LR, Brown R (1993) Cisplatin-DNA damage recognition proteins in human tumour extracts. Br J Cancer 67:742–748
Brown SJ, Kellett PJ, Lippard SJ (1993) Ixr1, a yeast protein that binds to platinated DNA and confers sensitivity to cisplatin. Science 261:603–605
Bruhn SL, Toney JH, Lippard SJ (1990) Biological processing of DNA modified by platinum compounds. Prog Inorg Chem 38:477–516
Bruhn SL, Pil PM, Essigmann JM, Housman DE, Lippard SJ (1992) Isolation and characterization of human cDNA clones encoding a high mobility group box protein that recognizes structural distortions to DNA caused by binding of the anticancer agent cisplatin. Proc Natl Acad Sci USA 89:2307–2311
Bruhn SL, Housman DE, Lippard SJ (1993) Isolation and characterization of cDNA clones encoding the Drosophila homolog of the HMG-box SSRP family that recognizes specific DNA structures. Nucleic Acids Res 21:1643–1646
Bustin M, Lehn DA, Landsman D (1990) Structural features of the HMG chromosomal proteins and their genes. Biochim Biophys Acta 1049:231–243
Chao CCK (1991) Potential negative regulation of damage-recognition proteins in cisplatin-resistant HeLa cells in response to DNA damage. Mutat Res 264:59–66
Chow CS, Whitehead JP, Lippard SJ (1994) HMG domain proteins induce sharp bends in cisplatin-modified DNA. Biochemistry 33:15124–15130
Chu G, Chang E (1988) Xeroderma pigmentosum group E cells lack a nuclear factor that binds to damaged DNA. Science 242:564–567
Ciccarelli RB, Solomon MJ, Varshavsky A, Lippard SJ (1985) In vivo effects of cis-and trans-diamminedichloroplatinum(II) on SV40 chromosomes: differential repair, DNA-protein cross-linking, and inhibition of replication. Biochemistry 24:7533–7540
Denny P, Swift S, Connor F, Ashworth A (1992) An SRY-related gene expressed during spermatogenesis in the mouse encodes a sequence-specific DNA-binding protein. EMBO J 11:3705–3712
Diffley JFX, Stillman B (1992) DNA binding properties of an HMG1-related protein from yeast mitochondria. J Biol Chem 267:3368–3374
Donahue BA, Augot M, Bellon SF, Treiber DK, Toney JF, Lippard SJ, Essigmann JM (1990) Characterization of a DNA damage-recognition protein from mammalian cells that binds specifically to intrastrand d(GpG) and d(ApG) DNA adducts of the anticancer drug cisplatin. Biochemistry 29:5872–5880
Dooijes D, van de Wetering M, Knippels L, Clevers H (1993) The Schizosaccharomyces pombe mating-type gene mat-Mc encodes a sequence-specific DNA-binding high mobility group box protein. J Biol Chem 268:24813–24817
Ferrari S, Harley VR, Pontiggia A, Goodfellow PN, Lovell-Badge R, Bianchi ME (1992) SRY, like HMG1, recognizes sharp angles in DNA. EMBO J 11:4497–4506
Fisher RP, Lisowsky T, Parisi MA, Clayton DA (1992) DNA wrapping and bending by a mitochondrial high mobility group-like transcriptional activator protein. J Biol Chem 267:3358–3367
Giese K, Grosschedl R (1993) LEF-1 contains an activation domain that stimulates transcription only in a specific context of factor-binding sites. EMBO J 12:4667–4676
Giese K, Cox J, Grosschedl R (1992) The HMG domain of Lymphoid Enhancer Factor 1 bends DNA and facilitates assembly of functional nucleoprotein structures. Cell 69:185–195
Giese K, Pagel J, Grosschedl R (1994) Distinct DNA-binding properties of the high mobility group domain of murine and human SRY sex-determining factors. Proc Natl Acad Sci USA 91:3368–3372
Grosschedl R, Giese K, Pagel J (1994) HMG domain proteins: architectural elements in the assembly of nucleoprotein structures. Trends Genet 10:94–100
Hamaguchi K, Godwin AK, Yakushiji M, O’Dwyer PJ, Ozols RF, Hamilton TC (1993) Cross-resistance to diverse drugs is associated with primary cisplatin resistance in ovarian cancer cell lines. Cancer Res 53:5225–5232
Haqq CM, King, CY, Donahoe PK, Weiss MA (1993) SRY recognizes conserved DNA sites in sex-specific promoters. Proc Natl Acad Sci USA 90:1097–1101
Hayes JJ, Scovell WM (1991a) cis-Diamminedichloroplatinum (II) modified chromatin and nucleosomal core particle probed with DNAse I. Biochim Biophys Acta 1088:413–418
Hayes J, Scovell WM (1991b) cis-Diamminedichloroplatinum (II) modified chromatin and nucleosomal core particle. Biochim Biophys Acta 1089:377–385
Hsu T, King DL, LaBonne C, Kafatos FC (1993) A Drosophila single-strand DNA/RNA-binding factor contains a high-mobility-group box and is enriched in the nucleolus. Proc Natl Acad Sci USA 90:6488–6492
Huang J-C, Zambie DB, Reardon JT, Lippard SJ, Sancar A (1994) HMG-domain proteins specifically inhibit the repair of the major DNA adduct of the anticancer drug cisplatin. Proc Natl Acad Sci USA 91:10394–10398
Hughes EN, Engelsberg BN, Billings PC (1992) Purification of nuclear proteins that bind to cisplatin damaged DNA: identity with high mobility group proteins 1 and 2. J Biol Chem 267:13520–13527
Jantzen HM, Admon A, Bell SP, Tjian R (1990) Nucleolar transcription factor hUBF contains a DNA-binding motif with homology to HMG proteins. Nature 344:830–836
King CY, Weiss MA (1993) The SRY high-mobility-group box recognizes DNA by partial intercalation in the minor groove: A topological mechanism of sequence specificity. Proc Natl Acad Sci USA 90:11990–11994
Kohlstaedt LA, Cole RD (1994) Specific interaction between H1 histone and High Mobility Protein HMG1. Biochemistry 33:570–575
Koopman P, Gubbay J, Vivian N, Goodfellow P, Lovell-Badge R (1991) Male development of chromosomally female mice transgenic for Sry. Nature 351:117–127
Kraulis PJ (1991) Molscript: a program to produce both detailed and schematic plots of protein structures. J Appl Crystallogr 24:946–950
Kuhn A, Voit R, Stefanovsky V, Evers R, Bianchi M, Grummt I (1994) Functional differences between the two splice variants of the nucleolar transcription factor UBF: the second HMG box determines specificity of DNA binding and transcriptional activity. EMBO J 13:416–424
Landsman D, Bustin M (1991) Assessment of the transcriptional activation potential of the HMG chromosomal proteins. Mol Cell Biol 11:4483–4489
Landsman D, Bustin M (1993) A signature for the HMG-1 box DNA-binding proteins. Bioessays 15:539–546
Lawrence DL, Engelsberg BN, Farid RS, Hughes EN, Billings PC (1993) Localization of the binding region of high mobility group protein 2 to cisplatin damaged DNA. J Biol Chem 268:23940–23945
Lippard SJ (1994) Structural and biological consequences of platinum anticancer drug binding to DNA. Proc Robert A Welch Foundation 37th Conf on Chemical Research, 40 years of the DNA double helix, October 1993 Chapt 4, pp 49-60
Maeda Y, Hisatake K, Kondo T, Hanada K, Song CZ, Nishimura T, Muramatsu M (1992) Mouse rRNA gene transcription factor mUBF requires both HMG-box 1 and an acidic tail for nucleolar accumulation: molecular analysis of the nucleolar targeting mechanism. EMBO J 11:3695–3704
Ner SS, Travers AA (1994) HMG-D, the Drosophila melanogaster homologue of HMG 1 protein, is associated with early embryonic chromatin in the absence of histone H1. EMBO J 13:1817–1822
Ner SS, Travers AA, Churchill MEA (1994) Harnessing the writhe: a role for DNA chaperones in nucleoprotein-complex formation. Trends Biochem Sci 19:185–187
Onate SA, Prendergast P, Wagner JP, Nissen M, Reeves R, Pettijohn DE, Edwards DP (1994) The DNA-bending protein HMG-1 enhances progesterone receptor binding to its target DNA sequences. Mol Cell Biol 14:3376–3391
Pauli TT, Haykinson MJ, Johnson RC (1993) The nonspecific DNA-binding and — bending proteins HMG1 and HMG2 promote the assembly of complex nucleoprotein structures. Genes Dev 7:1521–1534
Pil PM, Lippard SJ (1992) Specific binding of chromosomal protein HMG1 to DNA damaged by the anticancer drug cisplatin. Science 256:234–237
Pil PM, Chow CS, Lippard SJ (1993) High-mobility-group 1 protein mediates DNA bending as determined by ring closures. Proc Natl Acad Sci USA 90:9465–9469
Read CM, Cary PD, Crane-Robinson C, Driscoll PC, Norman DG (1993) Solution structure of a DNA-binding domain from HMG1. Nucleic Acids Res 21:3427–3436
Schnapp G, Santori F, Carles C, Riva M, Grummt I (1994) The HMG box-containing nucleolar transcription factor UBF interacts with a specific subunit of RNA Polymerase I. EMBO J 13:190–199
Scovell WM, Muirhead N, Kroos LR (1987) cis-Diamminedichloroplatinum(II) selectively cross-links high mobility group proteins 1 and 2 to DNA in micrococcal nuclease accessible regions of chromatin. Biochem Biophys Res Commun 142:826–835
Sheflin LG, Spaulding SW (1989) High Mobility Group protein 1 preferentially conserves torsion in negatively supercoiled DNA. Biochemistry 28:5658–5664
Sheflin LG, Fucile NW, Spaulding SW (1993) The specific interactions of HMG1 and 2 with negatively supercoiled DNA are modulated by their acidic C-terminal domains and involve cysteine residues in their HMG1/2 boxes. Biochemistry 32:3238–3248
Shirakata M, Huppi K, Usuda S, Okazaki K, Yoshida K, Sakano H (1991) HMG1-related DNA-binding protein isolated with V-(D)-J recombination signal probes. Mol Cell Biol 11:4528–4536
Shore D, Langowski J, Baldwin RL (1981) DNA flexibility studied by covalent closure of short fragments into circles. Proc Natl Acad Sci USA 78:4833–4837
Singh J, Dixon GH (1990) High Mobility Group proteins 1 and 2 function as general class II transcription factors. Biochemistry 29:6295–6302
Stolzenburg F, Dinkl E, Grummt F (1992) Nucleotide sequence of a mouse cDNA encoding the non-histone chromosomal high mobility group protein-2 (HMG-2). Nucleic Acids Res 20:4927
Stros M, Stokrova J, Thomas JO (1994) DNA looping by the HMG-box domains of HMG1 and modulation of DNA binding by the acidic C-terminal domain. Nucleic Acids Res 22:1044–1051
Sundquist WI, Lippard SJ, Stollar BD (1986) Binding of cis-and trans-diamminedichloroplatinum (II) to deoxyribonucleic acid exposes nucleosides as measured immunochemically with anti-nucleoside antibodies. Biochemistry 25:1520–1524
Szymkowski DE, Yarema K, Essigmann JM, Lippard SJ, Wood RD (1992) An intrastrand d(GpG) platinum crosslink in duplex M13 DNA is refractory to repair by human cell extracts. Proc Natl Acad Sci USA 89:10772–10776
Toney JH, Donahue BA, Kellett PJ, Bruhn SL, Essigmann JM, Lippard SJ (1989) Isolation of cDNAs encoding a human protein that binds selectively to DNA modified by the anticancer drug cis-diamminedichloroplatinum(II). Proc Natl Acad Sci USA 86:8328–8332
Travis A, Amsterdam A, Belanger C, Grosschedl R (1991) LEF-1, a gene encoding a lymphoid-specific with protein, an HMG domain, regulates T-cell receptor α enhancer function. Genes Dev 5:880–894
Treiber DK, Zhai X, Jantzen HM, Essigmann JM (1994) Cisplatin-DNA adducts are molecular decoys for the ribosomal RNA transcription factor hUBF (human upstream binding factor). Proc Natl Acad Sci USA 91:5672–5676
Tremethick DJ, Molloy PL (1988) Effects of high mobility group proteins 1 and 2 on initiation and elongation of specific transcription by RNA Polymerase II in vitro. Nucleic Acids Res 16:11107–11123
van de Wetering M, Clevers H (1992) Sequence-specific interaction of the HMG box proteins TCF-1 and SRY occurs within the minor groove of a Watson-Crick double helix. EMBO J 11:3039–3044
van de Wetering M, Oosterwegel M, van Norren K, Clevers H (1993) Sox4, an Srylike HMG box protein, is a transcriptional activator in lymphocytes. EMBO J 12:3847–3854
Waga S, Mizuno S, Yoshida M (1989) Nonhistone proteins HMG1 and HMG2 suppress the nucleosome assembly at physiological ionic strength. Biochim Biophys Acta 1007:209–214
Wang L, Precht P, Balakir R, Horton WE Jr (1993) Rat and chick cDNA clones encoding HMG-like proteins. Nucleic Acids Res 21:1493
Watt F, Molloy PL (1988) High mobility group proteins 1 and 2 stimulate binding of a specific transcription factor to the adenovirus major late promoter. Nucleic Acids Res 16:1471–1486
Weir HM, Kraulis PJ, Hill CS, Raine ARC, Laue ED, Thomas JO (1993) Structure of the HMG box motif in the B-domain of HMG1. EMBO J 12:1311–1319
Wu HM, Crothers DM (1984) The locus of sequence-directed and protein-induced DNA bending. Nature 308:509–513
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1995 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
McA’Nulty, M.M., Lippard, S.J. (1995). Consequences of HMG-Domain Protein Binding to Cisplatin-Modified DNA. In: Eckstein, F., Lilley, D.M.J. (eds) Nucleic Acids and Molecular Biology. Nucleic Acids and Molecular Biology, vol 9. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-79488-9_13
Download citation
DOI: https://doi.org/10.1007/978-3-642-79488-9_13
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-79490-2
Online ISBN: 978-3-642-79488-9
eBook Packages: Springer Book Archive