Blocking of DNA synthesis in vitro by a guanosine 2',3'-cyclic phosphate: a possible mechanism of chromosome aberrations induced by U5 snRNA.

K Hamada, K Yokoro

Index: Mutat. Res. 326(1) , 71-82, (1995)

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Abstract

U5 snRNA can induce both transformation and chromosome aberrations of cells. The polypurine tract, GGAGAGGAA, of the RNA has been suggested to participate in both phenomena. In vitro transcription expected to give this polypurine oligoribonucleotide was associated with cleavage of transcripts, generating 5'-terminal hydroxyl and 3'-terminal 2',3'-cyclic phosphate groups. The cleavage was further studied by making use of a Mg(2+)-catalyzed reaction and RNase T1 and RNase U2 digestion. The cleavage was found to generate highly reactive RNA molecules, participating in subsequent ligation of RNAs. Such a reactive molecule, guanosine-2',3'-cyclic phosphate, was capable of blocking DNA synthesis in vitro. The results may provide a possible mechanism of the chromosome aberrations induced by U5.