2-Chloro-2'-deoxyadenosine: alteration of DNA:TATA element binding protein (TBP) interactions.

2-Chloro-2'-deoxyadenosine (CldAdo, cladribine) is used therapeutically for hairy cell and other leukemias. The nucleoside is converted in leukemia cells to the 2-Cl-analog of dATP and incorporated into DNA, where it may alter binding of transcription factors to gene regulatory AT-rich sequences. Here we model the effects of CldATP incorporation into the adenovirus major late promoter TATA element recognized by TATA binding protein (TBP). The modeling results are consistent with experimental studies of DNA:TBP binding and indicate which positions in the canonical TATA sequence are most severely affected by CldATP incorporation.FIGURE Structure of the DNA:TBP complex. The protein is shown as a ribbon structure, and the DNA as a stick model