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Identification of functional domains in TdIF1 and its inhibitory mechanism for TdT activity
Author(s) -
Kubota Takashi,
Maezawa So,
Koiwai Kotaro,
Hayano Takahide,
Koiwai Osamu
Publication year - 2007
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2007.01105.x
Subject(s) - biology , mechanism (biology) , identification (biology) , inhibitory postsynaptic potential , computational biology , neuroscience , ecology , epistemology , philosophy
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 β‐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.