DNA topoisomerase II sites in the histone H4 gene during the highly synchronous cell cycle of Physarum polycephalum

Abstract

The nearly perfect synchrony of nuclear division in a plasmodium of Physarum polycephalum provides a powerful system to analyze topoisomerase II cleavage sites in the course of the cell cycle. The histone H4 locus, whose schedule of replication and transcription is precisely known, was chosen for this analysis. Drug-induced topoisomerase II sites are clustered downstream of the histone H4 gene and appear highly dependent on cell cycle stage. They were only detected in mitosis and at the very beginning of S phase, precisely at the time of replication of the histone H4 region. The sites, which were absent in G2 phase, reappeared at the next mitosis. Remarkably, DNase I hypersensitive sites occurred in nearly the same location, but their schedule was totally different: they were absent in mitosis and present in G2. This schedule follows H4 transcription, which peaks in mid-S phase and in the second part of G2 phase and is off during mitosis. These results suggest that topoisomerase II may not be involved in transcription, but plays a role in remodeling chromatin structure, both during chromosome condensation in prophase/metaphase to allow their decatenation and during chromosome decondensation after metaphase to allow replication fork passage throughout the region.

Cell cycle-dependent DNA damage signaling induced by ICRF-193 involves ATM, ATR, CHK2, and BRCA1

“…Chromosome decondensation initiates during the telophase of mitosis and continues throughout the G1 phase [43], which strongly suggests that the DNA damage induced by ICRF-193 during late mitosis/early G1 could be related to topo II activity during chromosome decondensation. The role of topo II in chromosome decondensation during normal cell cycle progression has only been reported in Physarum polycephalum [53]. Our results provide the first evidence in mammalian cells that topo II might be required for chromosome decondensation during the normal cell cycle.…”