Oncogenic potential of the DNA replication licensing protein CDT1.

The expression of a gene, designated as Retroviral insertion site (Ris)2, was activated by retroviral DNA integration in an immortalized primitive erythroid cell line, EB-PE. Ris2 was also expressed at high levels in all human tumor cell lines analysed. Consistently, NIH3T3 fibroblasts overexpressing Ris2 formed tumors in Rag2 -/- mice when injected subcutaneously. The putative RIS2 protein shows a high sequence similarity to Xenopus CDT1, Drosophila DUP, and human CDT1, a newly identified DNA replication licensing protein, suggesting that Ris2 is a mouse homologue of CDT1. Cells overexpressing Ris2/Cdt1 exhibited a quicker entry into S phase when released from serum starvation compared to controls. Our results suggest that CDT1, an essential licensing protein for DNA replication, can function as an oncogene in mammals.