A full-length cDNA clone for the human nuclear protein cyclin has been isolated by using polyclonal antibodies and sequenced. The sequence predicts a protein of 261 amino acids (Mr 29,261) with a high content of acidic (41, aspartic and glutamic acids) versus basic (24, lysine and arginine) amino acids. The identity of the cDNA clone was confirmed by in vitro hybrid-arrested translation of cyclin mRNA. Blot-hybridization analysis of mouse 3T3 and human MOLT-4 cell RNA revealed a mRNA species of approximately the same size as the cDNA insert. Expression of cyclin mRNA was undetectable or very low in quiescent cells, increasing after 8-10 hr of serum stimulation. Inhibition of DNA synthesis by hydroxyurea in serum-stimulated cells did not affect the increase in cyclin mRNA but inhibited 90% the expression of H3 mRNA. These results suggest that expression of cyclin and histone mRNAs are controlled by different mechanisms. A region of the cyclin sequence shows a significant homology with the putative DNA binding site of several proteins, specially with the transcriptional-regulator cAMP-binding protein of Escherichia coli, suggesting that cyclin could play a similar role in eukaryotic cells.The identification of the cellular proteins that are involved in the control of cell proliferation in normal cells is essential for understanding the mechanisms underlying growth regulation and cellular transformation. A nuclear protein, "cyclin" (Mr 36,000), whose synthesis correlates with the proliferative state of the cells, is potentially such a candidate (for reviews, see refs. 1 and 2). This protein is present in variable amounts in normal proliferating cells as well as transformed cells and tumors. It is highly conserved, as determined by onedimensional peptide mapping, and it has been identified in several cell types of human, mouse, hamster, and avian origin. The level of cyclin fluctuates during the cell cycle, with a clear increase during the S phase (3, 4). Moreover, a coordinate synthesis of cyclin and DNA has been demonstrated in serum or growth factor-induced quiescent cells (5, 6). The proliferating-cell nuclear antigen (PCNA; refs. 7-10), a human protein that shares the same properties, has been shown to be identical to cyclin (9, 11). Immunofluorescence studies of the distribution of cyclin (PCNA) during the cell cycle have revealed dramatic changes in its nuclear localization during the S phase (7,12,13). Recent studies have demonstrated that these changes are not triggered by a mechanism involving direct phosphorylation of cyclin (4) and that they depend on DNA synthesis or events during the S phase (12).To learn more about the structure and function of cyclin, we decided to isolate cDNA clones of the mRNA for cyclin. We report here the complete nucleotide sequence for human cyclin and its expression during the cell cycle. MATERIALS AND METHODSCells. Mouse 3T3 cells were routinely grown in Dulbecco's modified Eagle's medium supplemented with 5% fetal calf serum and antibiotics (penicillin, 100 units/ml...