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

Yan Ouyang, Jennifer Salstrom, Silvia Diaz-Perez, Shareef Nahas, Youko Matsuno, David Dawson, Michael A. Teitell, Steve Horvath, Arthur D. Riggs, Richard A. Gatti, York Marahrens

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)875-880
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number3
StatePublished - Nov 25 2005

Bibliographical note

Funding Information:
The authors thank Laura Gammill, Shaun Fouse, and Guoping Fan for critically reading the manuscript. ATR-kd and ATM-kd constructs were kindly provided by Robert Abraham (Burnham Institute, La Jolla, CA) and Michael Kastan (St. Jude Children’s Research Hospital, Memphis, TN), respectively. The human lymphoblastoid cell line expressing ATM-GFP was kindly provided by Susan Lees-Miller (University of Calgary, CA) and Kum Kum Khanna (Queensland Institute of Medical Research, AU). This work was supported by NIH R01 GM61007-01A1 (Y.M.), NIH R01 HD41451:01 (Y.M.), and by a grant from the Ataxia-Telangiectasia Medical Research Foundation.


  • 2-Aminopurine
  • ATM
  • ATR
  • Checkpoint
  • Heterochromatin
  • Inactive X chromosome


Dive into the research topics of 'Inhibition of Atm and/or Atr disrupts gene silencing on the inactive X chromosome'. Together they form a unique fingerprint.

Cite this