title: Heat-induced alterations of nuclear protein associations and their effects on DNA repair and replication.
abstract: New knowledge of nuclear structure and DNA repair pathways has provided the basis for new insight into the effects of hyperthermia on the proteins involved in these processes. The nucleus is made up of mega protein-nucleic acid complexes that conduct various nuclear functions, including DNA packing, repair, replication and transcription. Heat shocks (41-50 degrees C) cause unfolding of a number of nuclear proteins. Such unfolding changes protein associations within all of the intra-nuclear mega protein-nucleic acid complexes studied, with the exception that no alterations in the nucleosome-DNA bead and super bead complexes could be detected. This review will address heat effects on protein-nucleic acid complexes related to DNA replication and DNA repair. Heat-induced changes in DNA replication complexes can be related to the killing of S-phase cells by heat. The effects of heat on DNA repair foci, complexes involving MRE11, the nucleolus and on the complexes that anchor DNA to the nuclear matrix appear to contribute to radiosensitization as a function of increasing thermal dose. Thus, heat effects on these complexes can serve as molecular targets for the development of agents that can enhance the effectiveness of clinical thermal radiotherapy.
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, St Louis, MO 63108, USA. jrotiroti@wustl.edu
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Roti Roti
mesh_terms: D002453:Cell Cycle / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D006358:Hot Temperature; D006801:Humans; D046911:Macromolecular Substances; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D011489:Protein Denaturation
chemical_list: D046911:Macromolecular Substances; D009687:Nuclear Proteins