DETERMINATION OF THE HUMAN C-ABL CONSENSUS DNA-BINDING SITE

c-Abl tyrosine kinase, an essential protein of the cell cycle signalli ng pathways, is implicated in the regulation of RNA polymerase II acti vity, apoptosis and DNA repair. Its DNA binding activity is important for its biological functions. However, the molecular basis of c-Abl in teraction with DNA remains largely unclear. We delimited the human c-A bl DNA binding domain and identified its preferred binding site, 5'-A( A)/(C)AACAA(A)/(C). The central AAC motif is highly conserved and cons titutes the major core element in the binding sites. EMSAs and footpri nting experiments were performed to explore how the c-Abl fusion prote in recognizes specific sequences in DNA. (C) 1998 Federation of Europe an Biochemical Societies.