Reorganization of the DNA–nuclear matrix interactions in a 210 kb genomic region centered on c‐myc after DNA replication in vivo

Abstract

In the interphase nucleus of metazoan cells DNA is organized in supercoiled loops anchored to a nuclear matrix (NM). DNA loops are operationally classified in structural and facultative. Varied evidence indicates that DNA replication occurs in replication foci organized upon the NM and that structural DNA loops may correspond to the replicons in vivo. In normal rat liver the hepatocytes are arrested in G0 but synchronously re-enter the cell cycle after partial-hepatectomy leading to liver regeneration. Using this model we have previously determined that the DNA loops corresponding to a gene-rich genomic region move in a sequential fashion towards the NM during replication and then return to their original configuration in newly quiescent cells, once liver regeneration has been achieved. In the present work we determined the organization into structural DNA loops of a gene-poor region centered on c-myc and tracked-down its movement at the peak of S phase and after the return to cellular quiescence during and after liver regeneration. The results confirmed that looped DNA moves towards the NM during replication but in this case the configuration of the gene-poor region into DNA loops becomes reorganized and after replication only the loop containing c-myc resembles the original in the control G0 hepatocytes. Our results suggest that the local chromatin configuration around potentially active genes constraints the formation of specific structural DNA loops after DNA replication, while in non-coding regions the structural DNA loops are only loosely determined after DNA replication by structural constraints that modulate the DNA-NM interactions.

Studies on the Interaction Mechanism of Pyrene Derivatives with Human Tumor-Related DNA

“…It has been considered that the necessary step in the activation process of genotoxic carcinogens, perhaps after the metabolic activation, is their DNA interaction [ 10 ]. Due to gene damage or mutation, tumor cells would lose control and continue to grow [ 11 , 12 ]. Thus, we choose two double-strand DNA sequences in the promoter regions of C-myc oncogene and p53 tumor suppressor gene as targets.…”