BLM (the causative gene of Bloom syndrome) protein translocation into the nucleus by a nuclear localization signal

Biochem Biophys Res Commun. 1997 Nov 17;240(2):348-53. doi: 10.1006/bbrc.1997.7648.


Bloom syndrome (BS) is a rare genetic disorder characterized by small body size, sun sensitivity, immunodeficiency and a high predisposition to various types of cancer. BLM was identified as the causative gene for BS, and BLM protein is homologous to DNA helicase. There are two putative nuclear localization signals (NLSs) within amino acid residues 1334-1349 in the C-terminus of the BLM protein, which has the distinctive structure of two basic residue arms separated by a spacer. The entire coding or deleted BLM sequences of various sizes were ligated into an enhanced green fluorescent protein (EGFP) vector and transfected into HeLa cells. The EGFP vector harboring the entire BLM coding sequence was transported to the nucleus. The BLM protein truncated at 1341 amino acid, containing an intact helicase domain and only one proximal arm, was not transported to the nucleus. The BLM protein truncated at 1357 amino acid, containing an intact helicase domain and two arms, was transported to the nucleus. The EGFP vector harboring DNA fragments encoding a protein having only the distal arms of basic amino acids in the C-terminus was also transported to the nucleus. The truncated BLM proteins corresponding to previously reported mutated BLM proteins were retained in the cytoplasm or both the cytoplasm and the nucleus as was the EGFP vector with no insert. These results show that the BLM protein translocates into the nucleus and that the distal arm of the bipartite basic residues in the C-terminus of the BLM protein is essential for targeting the nucleus.

MeSH terms

  • Adenosine Triphosphatases / biosynthesis
  • Adenosine Triphosphatases / chemistry*
  • Adenosine Triphosphatases / metabolism*
  • Amino Acid Sequence
  • Bloom Syndrome / genetics*
  • Cell Nucleus / metabolism*
  • DNA Helicases / biosynthesis
  • DNA Helicases / chemistry*
  • DNA Helicases / metabolism*
  • DNA Primers
  • Green Fluorescent Proteins
  • HeLa Cells
  • Humans
  • Luminescent Proteins / analysis
  • Luminescent Proteins / biosynthesis
  • Molecular Sequence Data
  • Nuclear Localization Signals*
  • Polymerase Chain Reaction
  • RecQ Helicases
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Subcellular Fractions / metabolism
  • Transfection


  • DNA Primers
  • Luminescent Proteins
  • Nuclear Localization Signals
  • Recombinant Fusion Proteins
  • Green Fluorescent Proteins
  • Adenosine Triphosphatases
  • Bloom syndrome protein
  • DNA Helicases
  • RecQ Helicases