A NOVEL YEAST GENE-PRODUCT, G4P1, WITH A SPECIFIC AFFINITY FOR QUADRUPLEX NUCLEIC-ACIDS

G4 nucleic acids are four-stranded helical structures that are formed in vitro by nucleic acids that contain guanine tracts. These structure s anneal readily under physiological conditions and are unusually stab le once formed. G4 nucleic acids are thought to participate in telomer e function, retroviral genome dimerization, chromosome alignment durin g homologue pairing, and mitotic recombination, although the in vivo d emonstration of these structures in any of these situations has not ye t been achieved. Here we purify and characterize an activity from yeas t, G4p1, which has a high and specific affinity for G4 nucleic acids. G4p1 prefers substrates containing multiple G4 domains, has an equal a ffinity for parallel and antiparallel G4 structures, and binds equival ently to RNA and DNA in G4 form. The Keg for G4p1 binding to a G4 DNA oligomer is 5.0 x 10(8) M(-1) under near physiological conditions. G4p 1 was purified and shown to derive from a 42-kDa protein (p42). We hav e cloned and sequenced the gene encoding p42 and show it to encode a n ovel protein with a region significantly homologous to bacterial methi onyl-tRNA synthetase dimerization domains, We have reconstituted the G 4p1 binding activity with recombinant p42 and present evidence that G4 p1 is a homodimer of p42.