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Interplay between Ino80 and Swr1 chromatin remodeling enzymes regulates cell cycle checkpoint adaptationin response to DNA damage

¹ Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA; ² Department of Biological Sciences, University of Alaska Anchorage, Anchorage, Alaska 99508, USA

Ino80 and Swr1 are ATP-dependent chromatin remodeling enzymes that have been implicated in DNA repair. Here we show that Ino80 is required for cell cycle checkpoint adaptation in response to a persistent DNA double-strand break (DSB). The failure of cells lacking Ino80 to escape checkpoint arrest correlates with an inability to maintain high levels of histone H2AX phosphorylation and an increased incorporation of the Htz1p histone variant into chromatin surrounding the DSB. Inactivation of Swr1 eliminates this DNA damage-induced Htz1p incorporation and restores H2AX phosphorylation and checkpoint adaptation. We propose that Ino80 and Swr1 function antagonistically at chromatin surrounding a DSB, and that they regulate the incorporation of different histone H2A variants that can either promote or block cell cycle checkpoint adaptation.

[Keywords: Ino80; Swr1; Htz1; DNA repair; chromatin; checkpoint]

Received April 12, 2006; revised version accepted July 7, 2006.

E-MAIL craig.peterson{at}umassmed.edu; FAX (508) 856-5011.

Supplemental material is available at http://www.genesdev.org.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1440206.

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