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)


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.


Excision Repair Bend Angle High Mobility Group Protein Acidic Tail Human Cell Extract 
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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

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