RETINOBLASTOMA SUSCEPTIBILITY GENES CONTAIN 5' SEQUENCES WITH A HIGH PROPENSITY TO FORM GUANINE-TETRAD STRUCTURES

Retinoblastoma susceptibility genes contain significant runs of oligoguanine at their 5' ends. Oligonucleotides having these sequences underwent complex formation in the presence of sodium ions, in which there was association of four strands. Formation of this structure was completely prevented if guanine was replaced by 7-deazaguanine, indicating the importance of guanine N7 in the formation of the complex. Complex formation lead to protection of guanine N7 against methylation by dimethyl sulphate, but thymine bases located between oligoguanine blocks were reactive to osmium tetroxide. There was also some sensitivity to S1 nuclease to the 5' side of the oligoguanine block. The results show that the G-rich regions of the mouse and human retinoblastoma susceptibility genes have a propensity to undergo tetraplex formation of the kind demonstrated in the immunoglobulin switch region.