Identification of functional domains in TdIF1 and its inhibitory mechanism for TdT activity

Takashi Kubota, So Maezawa, Kotaro Koiwai, Takahide Hayano, Osamu Koiwai

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


TdT interacting factor 1 (TdIF1) was identified as a protein that binds to terminal deoxynucleotidyltransferase (TdT) to negatively regulate TdT activity. TdT is a template-independent DNA polymerase that catalyzes the incorporation of deoxynucleotides to the 3'-hydroxyl end of DNA templates to increase the junctional diversity of immunoglobulin or T-cell receptor (TcR) genes. Here, using bioinformatics analysis, we identified the TdT binding, DNA binding and dimerization regions, and nuclear localization signal (NLS) in TdIF1. TdIF1 bound to double-stranded DNA (dsDNA) through three DNA binding regions: residues 1-75, the AT-hook-like motif (ALM) and the predicted helix-turn-helix (HTH) motif. ALM in TdIF1 preferentially bound to AT-rich DNA regions. NLS was of the bipartite type and overlapped ALM. TdIF1 bound to the Pol beta-like region in TdT and blocked TdT access to DNA ends. In the presence of dsDNA, however, TdIF1 bound to dsDNA to release TdT from the TdIF1/TdT complex and to exhibit TdT activity, implying that active TdT released microenvironmentally concentrates around AT-rich DNA to synthesize DNA.

Original languageEnglish
Pages (from-to)941-959
Number of pages19
JournalGenes to Cells
Issue number8
Early online date27 Jul 2007
Publication statusPublished - Aug 2007


  • AT Rich Sequence
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Carrier Proteins
  • Cell Nucleus
  • DNA Nucleotidylexotransferase
  • DNA, Single-Stranded
  • DNA-Directed DNA Polymerase
  • Dimerization
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Nuclear Localization Signals
  • Nuclear Proteins
  • Protein Binding
  • Protein Structure, Tertiary
  • Sequence Alignment
  • Sequence Homology, Amino Acid


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