Heat induced ‘masking’ of redox sensitive component(s) of the DNA-nuclear matrix anchoring complex

The ‘masking effect’ is the observation that heat shock reduces or masks the apparent expression of ionizing radiation (IR) damage to DNA. The mechanism of this effect is thought to involve the aggregation of proteins to the nuclear matrix or chromatin, thereby stabilizing these structures and masking actual DNA damage from assays and presumably from DNA repair complexes. Previously, using the ‘halo assay’, it has been shown that nucleoids treated with 1 mm dithiothreitol (DTT) and/or IR inhibited the rewinding of DNA supercoils and that this effect was masked in nucloids isolated from heated cells. Here it is reported that treatment of living cells with reducing agents diminishes the interaction between DNA and Protein Disulphide Isomerase (PDI) and that hyperthermia restored the PDI-DNA interaction, indicating that the masking effect occurred in vivo. PDI is a nuclear matrix protein which binds MAR DNA sequences and may be involved in regulating the degree of DNA supercoiling. It is hypothesized that he...