Human alpha spectrin II and the Fanconi anemia proteins FANCA and FANCC interact to form a nuclear complex

J Biol Chem. 1999 Nov 12;274(46):32904-8. doi: 10.1074/jbc.274.46.32904.

Abstract

Fanconi anemia (FA) is a genetic disorder characterized by bone marrow failure, congenital abnormalities, cancer susceptibility, and a marked cellular hypersensitivity to DNA interstrand cross-linking agents, which correlates with a defect in ability to repair this type of damage. We have previously identified an approximately 230-kDa protein present in a nuclear protein complex in normal human lymphoblastoid cells that is involved in repair of DNA interstrand cross-links and shows reduced levels in FA-A cell nuclei. The FANCA gene appears to play a role in the stability or expression of this protein. We now show that p230 is a well known structural protein, human alpha spectrin II (alphaSpIISigma*), and that levels of alphaSpIISigma* are not only significantly reduced in FA-A cells but also in FA-B, FA-C and FA-D cells (i.e. in all FA cell lines tested), suggesting a role for these FA proteins in the stability or expression of alphaSpIISigma*. These studies also show that alphaSpIISigma* forms a complex in the nucleus with the FANCA and FANCC proteins. alphaSpIISigma* may thus act as a scaffold to align or enhance interactions between FA proteins and proteins involved in DNA repair. These results suggest that FA represents a disorder in which there is a deficiency in alphaSpIISigma*.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Blotting, Western
  • Cell Cycle Proteins*
  • Cell Line
  • DNA Repair
  • DNA-Binding Proteins*
  • Fanconi Anemia / genetics*
  • Fanconi Anemia Complementation Group A Protein
  • Fanconi Anemia Complementation Group C Protein
  • Fanconi Anemia Complementation Group Proteins
  • HeLa Cells
  • Humans
  • Nuclear Proteins / metabolism
  • Peptides / chemistry*
  • Peptides / deficiency
  • Precipitin Tests
  • Protein Binding
  • Proteins / metabolism*
  • Spectrin / deficiency
  • Spectrin / metabolism*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • FANCA protein, human
  • FANCC protein, human
  • Fanconi Anemia Complementation Group A Protein
  • Fanconi Anemia Complementation Group C Protein
  • Fanconi Anemia Complementation Group Proteins
  • Nuclear Proteins
  • Peptides
  • Proteins
  • p 230
  • Spectrin