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Published Online May 15, 2008
Science DOI: 10.1126/science.1159051

Reports

Submitted on April 14, 2008
Accepted on May 1, 2008

Activation of the Cellular DNA Damage Response in the Absence of DNA Lesions

Evi Soutoglou 1* and Tom Misteli 1*

1 National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

* To whom correspondence should be addressed.
Evi Soutoglou , E-mail: soutogle{at}mail.nih.gov
Tom Misteli , E-mail: mistelit{at}mail.nih.gov

The cellular DNA damage response (DDR) is initiated by the rapid recruitment of repair factors to the site of DNA damage to form a multiprotein repair complex. How the repair complex senses damaged DNA and then activates the DDR is not well understood. Here we demonstrate that prolonged binding of DNA repair factors to chromatin can elicit DDR in an ATM- and DNAPK-dependent fashion in the absence of DNA damage. Targeting of single repair factors to chromatin revealed a hierarchy of protein interactions within the repair complex and suggests amplification of the damage signal. We conclude that activation of DDR does not require DNA damage and stable association of repair factors with chromatin is likely a critical step in triggering, amplifying and maintaining the DDR signal.


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Science. ISSN 0036-8075 (print), 1095-9203 (online)