Papamichos-Chronakis Manolis, Krebs Jocelyn E, Peterson Craig L
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Genes Dev. 2006 Sep 1;20(17):2437-49. doi: 10.1101/gad.1440206.
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.
Ino80和Swr1是与DNA修复有关的ATP依赖性染色质重塑酶。我们在此表明，Ino80是细胞周期检查点适应持续性DNA双链断裂（DSB）所必需的。缺乏Ino80的细胞无法逃脱检查点停滞，这与无法维持高水平的组蛋白H2AX磷酸化以及Htz1p组蛋白变体增加掺入DSB周围的染色质有关。Swr1的失活消除了这种DNA损伤诱导的Htz1p掺入，并恢复了H2AX磷酸化和检查点适应。我们提出，Ino80和Swr1在DSB周围的染色质上发挥拮抗作用，并且它们调节不同组蛋白H2A变体的掺入，这些变体可以促进或阻断细胞周期检查点适应。
