PMID- 23237939
OWN - NLM
STAT- MEDLINE
DCOM- 20130617
LR  - 20131121
IS  - 1568-7856 (Electronic)
IS  - 1568-7856 (Linking)
VI  - 12
IP  - 1
DP  - 2013 Jan 1
TI  - Inhibition of homologous recombination by hyperthermia shunts early double strand 
      break repair to non-homologous end-joining.
PG  - 38-45
LID - S1568-7864(12)00264-9 [pii]
LID - 10.1016/j.dnarep.2012.10.008 [doi]
AB  - In S and G2 phase mammalian cells DNA double strand breaks (DSBs) can potentially 
      be repaired by homologous recombination (HR) or non-homologous end-joining 
      (NHEJ). Results of several studies suggest that these two mechanistically 
      distinct repair pathways can compete for DNA ends. Because HR and NHEJ differ 
      with respect to error susceptibility, generation of chromosome rearrangements, 
      which are potentially carcinogenic products of DSB repair, may depend on the 
      pathway choice. To investigate this hypothesis, the influence of HR and NHEJ 
      inhibition on the frequencies of chromosome aberrations in G2 phase cells was 
      investigated. SW-1573 and RKO cells were treated with mild (41  degrees C) hyperthermia 
      in order to disable HR and/or NU7441/cisplatin to inactivate NHEJ and frequencies 
      of chromosomal fragments (resulting from unrepaired DSBs) and translocations 
      (products of erroneous DSB rejoining) were studied using premature chromosome 
      condensation (PCC) combined with fluorescence in situ hybridization (FISH). It is 
      shown here that temporary inhibition of HR by hyperthermia results in increased 
      frequency of ionizing-radiation (IR)-induced chromosomal translocations and that 
      this effect is abrogated by NU7441- or cisplatin-mediated inhibition of NHEJ. The 
      results suggest that in the absence of HR, DSB repair is shifted to the 
      error-prone NHEJ pathway resulting in increased frequencies of chromosomal 
      rearrangements. These results might be of consequence for clinical cancer 
      treatment approaches that aim at inhibition of one or more DSB repair pathways.
CI  - Copyright (c) 2012 Elsevier B.V. All rights reserved.
FAU - Bergs, Judith W J
AU  - Bergs JW
AD  - Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for 
      Experimental Molecular Medicine, Department of Radiation Oncology, Academic 
      Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The 
      Netherlands.
FAU - Krawczyk, Przemek M
AU  - Krawczyk PM
FAU - Borovski, Tijana
AU  - Borovski T
FAU - ten Cate, Rosemarie
AU  - ten Cate R
FAU - Rodermond, Hans M
AU  - Rodermond HM
FAU - Stap, Jan
AU  - Stap J
FAU - Medema, Jan Paul
AU  - Medema JP
FAU - Haveman, Jaap
AU  - Haveman J
FAU - Essers, Jeroen
AU  - Essers J
FAU - van Bree, Chris
AU  - van Bree C
FAU - Stalpers, Lukas J A
AU  - Stalpers LJ
FAU - Kanaar, Roland
AU  - Kanaar R
FAU - Aten, Jacob A
AU  - Aten JA
FAU - Franken, Nicolaas A P
AU  - Franken NA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121211
PL  - Netherlands
TA  - DNA Repair (Amst)
JT  - DNA repair
JID - 101139138
RN  - 0 (8-dibenzothiophen-4-yl-2-morpholin-4-yl-chromen-4-one)
RN  - 0 (Chromones)
RN  - 0 (Morpholines)
RN  - Q20Q21Q62J (Cisplatin)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Chromones
MH  - Cisplatin/toxicity
MH  - DNA Breaks, Double-Stranded
MH  - *DNA End-Joining Repair
MH  - G2 Phase
MH  - Gamma Rays
MH  - *Homologous Recombination
MH  - *Hot Temperature
MH  - Humans
MH  - Mice
MH  - Morpholines
MH  - Radiation Tolerance
MH  - *Recombinational DNA Repair
MH  - Translocation, Genetic/drug effects/radiation effects
EDAT- 2012/12/15 06:00
MHDA- 2013/06/19 06:00
CRDT- 2012/12/15 06:00
PHST- 2011/11/10 00:00 [received]
PHST- 2012/10/11 00:00 [revised]
PHST- 2012/10/12 00:00 [accepted]
PHST- 2012/12/15 06:00 [entrez]
PHST- 2012/12/15 06:00 [pubmed]
PHST- 2013/06/19 06:00 [medline]
AID - S1568-7864(12)00264-9 [pii]
AID - 10.1016/j.dnarep.2012.10.008 [doi]
PST - ppublish
SO  - DNA Repair (Amst). 2013 Jan 1;12(1):38-45. doi: 10.1016/j.dnarep.2012.10.008. 
      Epub 2012 Dec 11.