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Open Access 01-12-2012 | Research

Increased Artemis levels confer radioresistance to both high and low LET radiation exposures

Authors: Deepa M Sridharan, Mary K Whalen, Donna Almendrala, Francis A Cucinotta, Misako Kawahara, Steven M Yannone, Janice M Pluth

Published in: Radiation Oncology | Issue 1/2012

Abstract

Background

Artemis has a defined role in V(D)J recombination and has been implicated in the repair of radiation induced double-strand breaks. However the exact function(s) of Artemis in DNA repair and its preferred substrate(s) in vivo remain undefined. Our previous work suggests that Artemis is important for the repair of complex DNA damage like that inflicted by high Linear Energy Transfer (LET) radiation. To establish the contribution of Artemis in repairing DNA damage caused by various radiation qualities, we evaluated the effect of over-expressing Artemis on cell survival, DNA repair, and cell cycle arrest after exposure to high and low LET radiation.

Results

Our data reveal that Artemis over-expression confers marked radioprotection against both types of radiation, although the radioprotective effect was greater following high LET radiation. Inhibitor studies reveal that the radioprotection imparted by Artemis is primarily dependent on DNA-PK activity, and to a lesser extent on ATM kinase activity. Together, these data suggest a DNA-PK dependent role for Artemis in the repair of complex DNA damage.

Conclusions

These findings indicate that Artemis levels significantly influence radiation toxicity in human cells and suggest that Artemis inhibition could be a practical target for adjuvant cancer therapies.

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Title: Increased Artemis levels confer radioresistance to both high and low LET radiation exposures
Authors: Deepa M Sridharan
Mary K Whalen
Donna Almendrala
Francis A Cucinotta
Misako Kawahara
Steven M Yannone
Janice M Pluth
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: Radiation Oncology / Issue 1/2012
Electronic ISSN: 1748-717X
DOI: https://doi.org/10.1186/1748-717X-7-96

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Increased Artemis levels confer radioresistance to both high and low LET radiation exposures

Abstract

Background

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Results

Conclusions

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