The effects of 41°C hyperthermia on the DNA repair protein, MRE11, correlate with radiosensitization in four human tumor cell lines

Abstract

These observations are consistent with the possibility that delocalization of MRE11 from the nucleus is a critical step in the radiosensitization by moderate hyperthermia.

Cell survival and radiosensitisation: Modulation of the linear and quadratic parameters of the LQ model

“…Translocation of the Mre11 DSB repair protein from the nucleus to the cytoplasm has also been implicated (106,111). However, disappearance of Mre11 protein foci at the sites of irradiation-induced DNA DSBs was not observed by pre-incubation of cells at 41˚C (24,27).…”

“…In a study by Xu et al, pre-treatment of cells at 41.1˚C for 1 h did not induce radiosensitisation, whereas treatment for 2 h or more resulted in radiosensitisation in the HT-resistant but not in the HT-sensitive cell line (106). However, simultaneous treatment of the sensitive cell line with 1-h 41.1˚C HT combined with irradiation increased cellular radiosensitivity (107).…”

Effects of hyperthermia on Hsp27 (HSPB1), Hsp72 (HSPA1A) and DNA repair proteins hMLH1 and hMSH2 in human colorectal cancer hMLH1-deficient and hMLH1-proficient cell lines

“…Interestingly our data showed that in HCT116 þ ch3 cells (MMR-proficient) hMLH1and hMSH2 proteins were released from the nucleus into the cytoplasm in response to heat shock. Previous studies showed that temperatures of 41 C or higher will drive out of the nucleus the repair protein MRE11 (component of the MRN complex involved in homologous recombination and non-homologous end joining) and lead to a subsequent sensitisation to ionising radiation [34,35]. This effect could be (C) Percentage of cells with severe DNA damage (score 3: 31-60% and score 4: 61-95%).…”

Radiosensitization with Hyperthermia and Chemotherapeutic Agents: Effects on Linear-Quadratic Parameters of Radiation Cell Survival Curves

“…Recently it was demonstrated that the BRCA-2 protein is transiently inhibited by mild hyperthermia (Krawzcyk et al, 2011). Also translocation of the Mre11 DSB repair protein from the nucleus to the cytoplasm has been implicated (Xu et al, 2002(Xu et al, , 2007. However, disappearance of Mre11 protein foci at the sites of irradiation induced DNA double strand breaks by 41ºC pre-incubation of cells was not observed (Krawzcyk et al, 2011;Bergs, 2007a).…”