Telomeric repeats on small polydisperse circular DNA (spcDNA) and genomic instability

Small polydisperse circular DNA (spcDNA) is a heterogeneous population of e xtrachromosomal circular molecules present in a large variety of eukaryotic cells. Elevated amounts of total spcDNA are related to endogenous and indu ced genomic instability in rodent and human cells, We suggested spcDNA as a novel marker for genomic instability, and speculated that spcDNA might ser ve as a mutator, In this study, we examine the presence of telomeric sequen ces on spcDNA, We report for the first time the appearance of telomeric rep eats in spcDNA molecules (tel-spcDNA) in rodent and human cells. Restrictio n enzyme analysis indicates that tel-spcDNA molecules harbor mostly, if not exclusively, telomeric repeats, In rodent cells, tel-spcDNA levels are hig her in transformed than in normal cells and are enhanced by treatment with carcinogen, Tel-spcDNA is also detected in some human tumors and cell lines , but not in others. We suggest, that its levels in human cells may be prim arily related to the amount of the chromosomal telomeric sequences. Tel-spc DNA may serve as a unique mutator, through specific mechanisms related to t he telomeric repeats, which distinguish it from the total heterogeneous spc DNA population. It may affect telomere dynamics and genomic instability by clastogenic events, alterations of telomere size and sequestration of telom eric proteins.