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Publication : Inhibition of Atm and/or Atr disrupts gene silencing on the inactive X chromosome.

First Author  Ouyang Y Year  2005
Journal  Biochem Biophys Res Commun Volume  337
Issue  3 Pages  875-80
PubMed ID  16213462 Mgi Jnum  J:102731
Mgi Id  MGI:3608013 Doi  10.1016/j.bbrc.2005.09.122
Citation  Ouyang Y, et al. (2005) Inhibition of Atm and/or Atr disrupts gene silencing on the inactive X chromosome. Biochem Biophys Res Commun 337(3):875-80
abstractText  ATM and ATR are well documented for their roles in maintaining the integrity of genomic DNA by responding to DNA damage and preparing the cell for repair. Since ATM and ATR have been reported to exist in complexes with histone deacetylases, we asked whether Atm and Atr might also uphold gene silencing by heterochromatin. We show that the Atm/Atr inhibitor 2-aminopurine causes the inactive X chromosome to accumulate abnormal chromatin and undergo unwanted gene reactivation. We provide evidence that this gene expression from the inactive X chromosome is not a byproduct of the accumulation of DNA breaks. Individually inhibiting Atm and Atr by either small interfering RNA or the expression of dominant-negative ATM and ATR constructs also compromised X-inactivation. Atm and Atr, therefore, not only function in responding to DNA damage but perhaps also are involved in gene silencing via the maintenance of heterochromatin.
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