The identification of nuclear proteins that bind the homopyrimidine strandof d(GA center dot TC)n DNA sequences, but not the homopurine strand

Alternating d(GA . TC)(n) DNA sequences, which are abundant in eukaryotic g enomes, can form altered DNA structures, Depending on the environmental con ditions, the formation of (GA . GA) hairpins or [C+T(GA . TC)] and [GA(GA . TC)] intramolecular triplexes was observed in vitro. In vivo, the formatio n of these non-B-DNA structures would likely require the contribution of sp ecific stabilizing factors, Here, we show that Friend's nuclear extracts ar e rich in proteins which bind the pyrimidine d(TC)(n) strand but not the pu rine d(GA)(n) strand (NOGA proteins), Upon chromatographic fractionation, f our major proteins were detected (NOGA1-4) that have been purified and char acterized, Purified NOGAs bind single-stranded d(TC)(n) with high affinity and specificity, showing no significant affinity for either d(GA), or d(GA . TC)(n) DNA sequences. We also show that NOGA1, -2 and -3, which constitut e the three most abundant and specific NOGA proteins, correspond to the sin gle-stranded nucleic acid binding proteins hnRNP-L, -K and -I, respectively . These results are discussed in the context of the possible contribution o f the NOGA proteins to the stabilization of the (GA . GA) and [GA(GA . TC)] conformers of the d(GA . TC)(n) DNA sequences.