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

Radiation Oncology

Janice M Pluth²  Steven M Yannone²  Misako Kawahara²  Francis A Cucinotta¹  Donna Almendrala²  Mary K Whalen²  Deepa M Sridharan² 

[1] NASA, Lyndon B. Johnson Space Center, 2101 NASA Parkway, Houston, TX 77058, USA;Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA

关键词: High LET radiation;    Radioresistance;    Artemis;   

Others  :  1160820
DOI  :  10.1186/1748-717X-7-96

 received in 2012-01-21, accepted in 2012-05-18,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Sridharan et al; licensee BioMed Central Ltd.

【 图 表 】

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