Gieseler F, Boege F, Clark M
Medizinische Poliklinik, University of Würzburg, Federal Republic of Germany.
Environ Health Perspect. 1990 Aug;88:183-5. doi: 10.1289/ehp.9088183.
The inhibition of differentiation and persistence of proliferation in cell transformation is probably not only caused by the mutation of single genes. An additional mechanism of transcriptional control, not only of single genes but of gene programs, is possibly the alteration of the topoisomerases. These enzymes regulate the conformation of DNA by twisting and unwinding the double strands. As has been shown previously, only the genes located in relaxed DNA areas are transcribed and, therefore, the topoisomerases can be described as a gene regulation device. We present the hypothesis that topoisomerase II action is not only altered in, but also necessary for, HL-60 granulocytic cell differentiation. Thus, alteration of topoisomerases may well be a molecular mechanism of cellular differentiation.
细胞转化过程中分化的抑制和增殖的持续可能不仅仅是由单个基因突变引起的。一种转录控制的额外机制，不仅涉及单个基因，还涉及基因程序，可能是拓扑异构酶的改变。这些酶通过扭曲和解开双链来调节DNA的构象。如先前所示，只有位于松弛DNA区域的基因才会被转录，因此，拓扑异构酶可被描述为一种基因调控装置。我们提出一个假说，即拓扑异构酶II的作用不仅在HL-60粒细胞分化过程中发生改变，而且对其分化是必要的。因此，拓扑异构酶的改变很可能是细胞分化的一种分子机制。
