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Findings on the Dissasemblage of Particular Nuclear Subdomain in Tumor Cells

Findings on the Dissasemblage of Particular Nuclear Subdomain in Tumor Cells

The authors discuss the particulars of the perinucluear compartment in DNA and its effects on the DNA integrity of a tumor rich environment. Human Topo I Antibody provided by TopoGEN.

Article Source: The Journal of Biological Chemistry

The Perinucleolar Compartment Is Directly Associated with DNA

Abstract
The perinucleolar compartment (PNC) is a nuclear subdomain that is unique to tumor cells, and the percentage of cells in a population containing PNCs (PNC prevalence) indicates the level of malignancy of that population. Here, we utilize anticancer drugs and other exogenous stimuli to investigate the structure and function of the PNC. Screening of clinically used anti-cancer drugs revealed two types of drugs disassemble PNCs and do so through their specific molecular actions. Transcriptioninhibitors reduce PNC prevalence in parallel with RNA polymerase III transcription reduction, and a subset of DNA-damaging drugs and stimuli (UV radiation) disassemble the PNC. Inhibition of cellular DNA damage response demonstrated that the DNA damage itself, not the response or polymerase III inhibition, is responsible for PNC disassembly, suggesting that the maintenance of the PNC is dependent upon DNA integrity. Analyses of the types of DNA damage that cause PNC disassembly show that interstrand DNAbase pairing, not strand continuity, is important for PNC integrity, indicating that the PNC components are directly interacting with the DNA. Complementary cell biology experiments demonstrated that the number of PNCs per cell increases with the rounds of endoreplication and that PNCs split into doublets during mid S phase, both of which are phenotypes that are typical of a replicating DNA loci. Together, these studies validate PNC disassembly as a screening marker to identify chemical probes and revealed that the PNC is directly nucleated on a DNA locus, suggesting a potential role for the PNC in gene expression regulation.

THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 284, NO. 7, pp. 4090–4101, February 13, 2009 doi: 10.1074/jbc.M807255200

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