Cell cycle-dependent regulation of the mouse DNA topoisomerase II alpha gene promoter

Expression of DNA topoisomerase (topo) II alpha varies through the cell cycle with its peak in G(2)/M. To investigate the mechanism controlling the topo II alpha gene expression, we cloned the 5' upstream region of the mouse topo II alpha 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 G(1) by treatment with mimosine, in S with thymidine, or in G(2)/M with colcemid. We found that the topo II alpha gene promoter has the cell cycle-dependent activity, which is low in G(1), rises in S, and peaks in G(2)/M. We suggest that the level of topo II alpha mRNA is determined by the cell cycle-regulated promoter. (C) 1997 Academic Press