Effects of heat shock on the Mre11/Rad50/Nbs1 complex in irradiated or unirradiated cells.
The mechanism by which hyperthermia sensitizes mammalian cells to ionizing radiation remains to be elucidated, but an overwhelming amount of circumstantial evidence suggests that heat radiosensitization might be mediated by inhibition of double-strand break repair, particularly after exposure of irradiated cells to heat treatments in excess of about 43 degrees C. In mammalian cells, double-strand break repair usually occurs via two pathways, non-homologous end-joining and homologous recombination. Several reports suggest a role for non-homologous end-joining in heat radiosensitization, while others implicate homologous recombination as a target. However, cell lines that are compromised in either the non-homologous end-joining or homologous recombination pathway are still capable of being radiosensitized, suggesting that heat affects both pathways. Indeed, several of the proteins involved in one or both of these pathways have been observed to undergo alterations or translocation after unirradiated or irradiated cells are exposed to heat shock. The work summarized in this review implicates proteins of the Mre11/Rad50/Nbs1 complex as targets for heat radiosensitization.
Dynlacht
J R
JR
Department of Radiation Oncology, Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. jdynlach@iupui.edu
Xu
M
M
Pandita
R K
RK
Wetzel
E A
EA
Roti Roti
J L
JL
D017766:Acid Anhydride Hydrolases; D000818:Animals; D018797:Cell Cycle Proteins / Q000502:physiology*; D002460:Cell Line / Q000502:physiology / Q000528:radiation effects; D045643:DNA Repair Enzymes / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D018869:Heat-Shock Response / Q000502:physiology*; D006801:Humans; D006979:Hyperthermia, Induced; D000076228:MRE11 Homologue Protein; D009687:Nuclear Proteins / Q000502:physiology*; D011836:Radiation Tolerance / Q000502:physiology*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C121766:MRE11 protein, human; C112156:NBN protein, human; D009687:Nuclear Proteins; D000076228:MRE11 Homologue Protein; D017766:Acid Anhydride Hydrolases; C112158:RAD50 protein, human; D045643:DNA Repair Enzymes