Cell cycle-dependent regulation of the mouse DNA topoisomerase IIalpha gene promoter.

Expression of DNA topoisomerase (topo) IIalpha varies through the cell cycle with its peak in G2/M. To investigate the mechanism controlling the topo IIalpha gene expression, we cloned the 5' upstream region of the mouse topo IIalpha gene. Although there was no TATA-like sequence, two GC and seven CCAAT boxes were found in the upstream region 5' distal to the major transcription start sites, which were located 137, 124, and 105 bp upstream from the ATG start codon. Luciferase vectors with the upstream sequences were constructed and transfected into HeLa cells, followed by cell cycle arrest either in G1 by treatment with mimosine, in S with thymidine, or in G2/M with colcemid. We found that the topo IIalpha gene promoter has the cell cycle-dependent activity, which is low in G1, rises in S, and peaks in G2/M. We suggest that the level of topo IIalpha mRNA is determined by the cell cycle-regulated promoter.