Two differentially spliced forms of topoisomerase IIalpha and beta mRNAs are conserved between birds and humans

Screening of chicken cDNA libraries has identified four distinct forms of topoisomerase IIalpha and beta cDNAs. Two of these, designated topo IIalpha-1 and topo IIbeta-1, were previously deposited in the database. The other two, topo IIalpha-2 and topo IIbeta-2, are novel variants that appear to be conserved between chicken and human. Topo IIalpha-2 encodes a protein with an additional 35 amino acids inserted after K321 of the chicken topo IIalpha-1 protein sequence. Topo IIbeta-2 encodes a protein missing 86 amino acids following V27 in the topo IIbeta-1 protein sequence. We have also detected several alternatively spliced forms of human topo IIalpha. One of these, topo IIalpha-3, appears to correspond to chicken topo IIalpha-2. The other two are novel. The existence of these alternatively spliced forms in mature cytoplasmic RNA was confirmed by RT-PCR in several cell lines. Interestingly, these alternatively spliced forms carry sites for post-translational modification, suggesting that they may be subject to differential regulation from the canonical forms. These results suggest that cells express a more complex repertoire of topo II isoforms than previously thought, raising the possibility that different forms of topo II may fulfil specialized functions in chromosome dynamics.