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Author

Kwon, H. Moo
Inflammation and Kidney Disorder Lab
Research Interests
  • TonEBP, Obesity, Cancer, Chronic inflammatory diseases, Brain disorder, Kidney disorders, Genomic instability

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Mre11-Rad50-Nbs1 complex is activated by hypertonicity

Cited 11 times inthomson ciCited 9 times inthomson ci
Title
Mre11-Rad50-Nbs1 complex is activated by hypertonicity
Author
Sheen, Mee RieKim, Seung WhanJung, Ju-YoungAhn, Joon YoungRhee, Juong G.Kwon, H. MooWoo, Seung Kyoon
Keywords
ATM; Cell cycle checkpoint; Chk2; DNA repair; Double-strand DNA breaks; Histone H2AX; Renal medulla
Issue Date
200611
Publisher
AMER PHYSIOLOGICAL SOC
Citation
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, v.291, no.5, pp.F1014 - F1020
Abstract
When exposed to hypertonic conditions, cells accumulate double-strand DNA breaks (DSBs) like they are exposed to ionizing radiation. It has been proposed that inactivation of the Mre11-Rad50-Nbs1 (MRN) complex due to nuclear exit is responsible for the accumulation of DSBs as cells fail to repair DSBs produced during normal cellular activity. In this study, we examined the MRN complex in cells switched to hypertonicity. Surprisingly, we found that the MRN complex stayed in the nucleus and remained intact in response to hypertonicity. In fact, the MRN complex was dramatically activated after 4 h of switch to hypertonicity in a dose-dependent manner as shown by formation of foci. Activation of ATM and the MRN complex by hypertonicity and bleomycin was additive as was activation of their downstream targets including γH2AX and Chk2 indicating that the cellular response to DSB was intact in hypertonic conditions. Activation of Chk2 in response to hypertonicity was not observed in mutant cells with functionally impaired MRN complex confirming that they are in the same pathway. After 20 h of a switch to hypertonicity, MRN foci and γH2AX returned to a control level, suggesting that cells adapted to hypertonicity by repairing DNA. We conclude that cells respond normally to DSB and repair the DNA damages induced by hypertonicity.
URI
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DOI
http://dx.doi.org/10.1152/ajprenal.00153.2006
ISSN
1931-857X
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