Functional compatibility between isoform α and β of type II DNA topoisomerase

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Abstract
DNA topoisomerase II (topo II) plays a crucial role in controlling the conformation of both DNA and whole chromosomes. This activity is essential for several cellular events such as DNA replication, transcription, chromosome condensation and segregation. In mammals, two genes code for isoforms of topo II, termed α and β. They are similar in primary structure and have almost identical catalytic properties in vitro. We transfected HeLa cells with small interfering RNAs (siRNAs) targeted against either topo IIα or IIβ, and succeeded in knocking down the expression of the corresponding protein. Chromosomes were condensed and aligned at metaphase in topo IIα-knockdown cells. Although some lagging chromosomes were observed, they were still segregated at anaphase despite the absence of topo IIα. When both topo IIα and topo IIγ were removed, the segregation of chromosomes was severely arrested, suggesting that topo IIγ could partially substitute for topo IIα. Double-knockdown experiments also revealed that topo II was required for shortening of the chromosome axis.