ICRF-193, AN INHIBITOR OF TOPOISOMERASE-II, DEMONSTRATES THAT DNA-REPLICATION IN SPERM NUCLEI RECONSTITUTED IN XENOPUS EGG EXTRACTS DOES NOT REQUIRE CHROMATIN DECONDENSATION

A bis(2,6-dioxopiperazine) derivative, ICRF-193, is a specific inhibit or of topoisomerase II without cleavable complex-stabilizing activity. In Xenopus egg extract containing ICRF-193, demembranated sperm head chromatins were inhibited from decondensation. However, nuclear envelo pe-lamina assembled on the inhibited chromatins. The nuclear envelope- lamina continued to expand even after loss of contact with the chromat in surface. On the other hand, semiconservative DNA replication was in itiated as soon as the lamina was assembled onto the surface of conden sed chromatin, though the initiation was retarded and its extent was r educed, compared with that in noninhibited chromatins. Thus, it is con cluded that topoisomerase II activity is not required for the formatio n of active DNA replication clusters and the extension of nuclear enve lope-lamina on the chromatin, while the nuclear envelope-mediated deco ndensation of sperm chromatins is dependent on topoisomerase II activi ty. (C) 1995 Academic Press, Inc.