Roti Roti Joseph L
Department of Radiation Oncology, Washington University School of Medicine, St Louis, MO 63108, USA.
Int J Hyperthermia. 2007 Feb;23(1):3-15. doi: 10.1080/02656730601091759.
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.
核结构和DNA修复途径的新知识为深入了解热疗对这些过程中相关蛋白质的影响提供了基础。细胞核由执行各种核功能的巨型蛋白质 - 核酸复合物组成，这些功能包括DNA包装、修复、复制和转录。热休克（41 - 50摄氏度）会导致许多核蛋白展开。这种展开改变了所有已研究的核内巨型蛋白质 - 核酸复合物中的蛋白质结合情况，但核小体 - DNA珠和超珠复合物未检测到变化。本综述将探讨热对与DNA复制和DNA修复相关的蛋白质 - 核酸复合物的影响。热诱导的DNA复制复合物变化可能与热对S期细胞的杀伤有关。热对DNA修复位点、涉及MRE11的复合物、核仁以及将DNA锚定到核基质的复合物的影响似乎随着热剂量的增加而导致放射增敏作用。因此，热对这些复合物的影响可作为开发能够提高临床热放疗效果的药物的分子靶点。
