Advertisement

Consequences of HMG-Domain Protein Binding to Cisplatin-Modified DNA

  • M. M. McA’Nulty
  • S. J. Lippard
Part of the Nucleic Acids and Molecular Biology book series (NUCLEIC, volume 9)

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.

Keywords

Excision Repair Bend Angle High Mobility Group Protein Acidic Tail Human Cell Extract 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 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 35:179–188PubMedCrossRefGoogle Scholar
  2. Bellon SF, Coleman JH, Lippard SJ (1991) DNA unwinding produced by sitespecific intrastrand cross-links of the antitumor drug cis-diamminedichloroplatinum (II). Biochemistry 30:8026–8035PubMedCrossRefGoogle Scholar
  3. 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 188:1286–1294PubMedCrossRefGoogle Scholar
  4. Bissett D, McLaughlin K, Kelland LR, Brown R (1993) Cisplatin-DNA damage recognition proteins in human tumour extracts. Br J Cancer 67:742–748PubMedCrossRefGoogle Scholar
  5. Brown SJ, Kellett PJ, Lippard SJ (1993) Ixr1, a yeast protein that binds to platinated DNA and confers sensitivity to cisplatin. Science 261:603–605PubMedCrossRefGoogle Scholar
  6. Bruhn SL, Toney JH, Lippard SJ (1990) Biological processing of DNA modified by platinum compounds. Prog Inorg Chem 38:477–516CrossRefGoogle Scholar
  7. 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 89:2307–2311PubMedCrossRefGoogle Scholar
  8. 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 21:1643–1646PubMedCrossRefGoogle Scholar
  9. Bustin M, Lehn DA, Landsman D (1990) Structural features of the HMG chromosomal proteins and their genes. Biochim Biophys Acta 1049:231–243PubMedGoogle Scholar
  10. Chao CCK (1991) Potential negative regulation of damage-recognition proteins in cisplatin-resistant HeLa cells in response to DNA damage. Mutat Res 264:59–66PubMedCrossRefGoogle Scholar
  11. Chow CS, Whitehead JP, Lippard SJ (1994) HMG domain proteins induce sharp bends in cisplatin-modified DNA. Biochemistry 33:15124–15130PubMedCrossRefGoogle Scholar
  12. Chu G, Chang E (1988) Xeroderma pigmentosum group E cells lack a nuclear factor that binds to damaged DNA. Science 242:564–567PubMedCrossRefGoogle Scholar
  13. 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 24:7533–7540PubMedCrossRefGoogle Scholar
  14. 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 11:3705–3712PubMedGoogle Scholar
  15. Diffley JFX, Stillman B (1992) DNA binding properties of an HMG1-related protein from yeast mitochondria. J Biol Chem 267:3368–3374PubMedGoogle Scholar
  16. 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 29:5872–5880PubMedCrossRefGoogle Scholar
  17. 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 268:24813–24817PubMedGoogle Scholar
  18. Ferrari S, Harley VR, Pontiggia A, Goodfellow PN, Lovell-Badge R, Bianchi ME (1992) SRY, like HMG1, recognizes sharp angles in DNA. EMBO J 11:4497–4506PubMedGoogle Scholar
  19. 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 267:3358–3367PubMedGoogle Scholar
  20. 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 12:4667–4676PubMedGoogle Scholar
  21. 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 69:185–195PubMedCrossRefGoogle Scholar
  22. 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 91:3368–3372PubMedCrossRefGoogle Scholar
  23. Grosschedl R, Giese K, Pagel J (1994) HMG domain proteins: architectural elements in the assembly of nucleoprotein structures. Trends Genet 10:94–100PubMedCrossRefGoogle Scholar
  24. 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 53:5225–5232PubMedGoogle Scholar
  25. Haqq CM, King, CY, Donahoe PK, Weiss MA (1993) SRY recognizes conserved DNA sites in sex-specific promoters. Proc Natl Acad Sci USA 90:1097–1101PubMedCrossRefGoogle Scholar
  26. Hayes JJ, Scovell WM (1991a) cis-Diamminedichloroplatinum (II) modified chromatin and nucleosomal core particle probed with DNAse I. Biochim Biophys Acta 1088:413–418PubMedGoogle Scholar
  27. Hayes J, Scovell WM (1991b) cis-Diamminedichloroplatinum (II) modified chromatin and nucleosomal core particle. Biochim Biophys Acta 1089:377–385PubMedGoogle Scholar
  28. 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 90:6488–6492PubMedCrossRefGoogle Scholar
  29. 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 91:10394–10398PubMedCrossRefGoogle Scholar
  30. 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 267:13520–13527PubMedGoogle Scholar
  31. Jantzen HM, Admon A, Bell SP, Tjian R (1990) Nucleolar transcription factor hUBF contains a DNA-binding motif with homology to HMG proteins. Nature 344:830–836PubMedCrossRefGoogle Scholar
  32. 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 90:11990–11994PubMedCrossRefGoogle Scholar
  33. Kohlstaedt LA, Cole RD (1994) Specific interaction between H1 histone and High Mobility Protein HMG1. Biochemistry 33:570–575PubMedCrossRefGoogle Scholar
  34. Koopman P, Gubbay J, Vivian N, Goodfellow P, Lovell-Badge R (1991) Male development of chromosomally female mice transgenic for Sry. Nature 351:117–127PubMedCrossRefGoogle Scholar
  35. Kraulis PJ (1991) Molscript: a program to produce both detailed and schematic plots of protein structures. J Appl Crystallogr 24:946–950CrossRefGoogle Scholar
  36. 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 13:416–424PubMedGoogle Scholar
  37. Landsman D, Bustin M (1991) Assessment of the transcriptional activation potential of the HMG chromosomal proteins. Mol Cell Biol 11:4483–4489PubMedGoogle Scholar
  38. Landsman D, Bustin M (1993) A signature for the HMG-1 box DNA-binding proteins. Bioessays 15:539–546PubMedCrossRefGoogle Scholar
  39. 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 268:23940–23945PubMedGoogle Scholar
  40. 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 49-60Google Scholar
  41. 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 11:3695–3704PubMedGoogle Scholar
  42. 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 13:1817–1822PubMedGoogle Scholar
  43. Ner SS, Travers AA, Churchill MEA (1994) Harnessing the writhe: a role for DNA chaperones in nucleoprotein-complex formation. Trends Biochem Sci 19:185–187PubMedCrossRefGoogle Scholar
  44. 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 14:3376–3391PubMedGoogle Scholar
  45. 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 7:1521–1534CrossRefGoogle Scholar
  46. Pil PM, Lippard SJ (1992) Specific binding of chromosomal protein HMG1 to DNA damaged by the anticancer drug cisplatin. Science 256:234–237PubMedCrossRefGoogle Scholar
  47. 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 90:9465–9469PubMedCrossRefGoogle Scholar
  48. Read CM, Cary PD, Crane-Robinson C, Driscoll PC, Norman DG (1993) Solution structure of a DNA-binding domain from HMG1. Nucleic Acids Res 21:3427–3436PubMedCrossRefGoogle Scholar
  49. 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 13:190–199PubMedGoogle Scholar
  50. 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 142:826–835PubMedCrossRefGoogle Scholar
  51. Sheflin LG, Spaulding SW (1989) High Mobility Group protein 1 preferentially conserves torsion in negatively supercoiled DNA. Biochemistry 28:5658–5664PubMedCrossRefGoogle Scholar
  52. 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 32:3238–3248PubMedCrossRefGoogle Scholar
  53. 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 11:4528–4536PubMedGoogle Scholar
  54. Shore D, Langowski J, Baldwin RL (1981) DNA flexibility studied by covalent closure of short fragments into circles. Proc Natl Acad Sci USA 78:4833–4837PubMedCrossRefGoogle Scholar
  55. Singh J, Dixon GH (1990) High Mobility Group proteins 1 and 2 function as general class II transcription factors. Biochemistry 29:6295–6302PubMedCrossRefGoogle Scholar
  56. 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 20:4927PubMedCrossRefGoogle Scholar
  57. 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 22:1044–1051PubMedCrossRefGoogle Scholar
  58. 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 25:1520–1524PubMedCrossRefGoogle Scholar
  59. 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 89:10772–10776PubMedCrossRefGoogle Scholar
  60. 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 86:8328–8332PubMedCrossRefGoogle Scholar
  61. 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 5:880–894PubMedCrossRefGoogle Scholar
  62. 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 91:5672–5676PubMedCrossRefGoogle Scholar
  63. 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 16:11107–11123PubMedCrossRefGoogle Scholar
  64. 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 11:3039–3044PubMedGoogle Scholar
  65. 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 12:3847–3854PubMedGoogle Scholar
  66. Waga S, Mizuno S, Yoshida M (1989) Nonhistone proteins HMG1 and HMG2 suppress the nucleosome assembly at physiological ionic strength. Biochim Biophys Acta 1007:209–214PubMedGoogle Scholar
  67. Wang L, Precht P, Balakir R, Horton WE Jr (1993) Rat and chick cDNA clones encoding HMG-like proteins. Nucleic Acids Res 21:1493PubMedCrossRefGoogle Scholar
  68. 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 16:1471–1486PubMedCrossRefGoogle Scholar
  69. 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 12:1311–1319PubMedGoogle Scholar
  70. Wu HM, Crothers DM (1984) The locus of sequence-directed and protein-induced DNA bending. Nature 308:509–513PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • M. M. McA’Nulty
    • 1
  • S. J. Lippard
    • 1
  1. 1.Department of ChemistryMassachusetts Institute of TechnologyCambridgeUSA

Personalised recommendations