Department of Molecular Science and Technology, College of Natural Sciences, Ajou University, Suwon, Republic of Korea.
FEBS Lett. 2011 Jan 3;585(1):47-52. doi: 10.1016/j.febslet.2010.11.034. Epub 2010 Nov 23.
The role of p300 in DNA damage response is unclear. To understand how ATM-dependent phosphorylation of p300 affects its function in response to DNA damage, we present evidence that S106 of p300, which is phosphorylated by ATM, regulates stability of NBS1 and recruitment into damaged DNA, possibly leading to regulation of DNA repair. Non-phosphorylatable p300 (S106A) destabilized NBS1 and decreased NBS1-p300 interaction. The recruitment of NBS1 into damaged DNA was impaired in the presence of S106A. Also, a dominant negative p300 lacking enzymatic activity induced destabilization of NBS1, suggesting that its acetyltransferase is required for NBS1 stability. These results indicate that phosphorylation of p300 can regulate NBS1-mediated DNA damage response, and that these events occur in an acetylation-dependent manner.
p300 在 DNA 损伤反应中的作用尚不清楚。为了了解 ATM 依赖性磷酸化 p300 如何影响其在 DNA 损伤反应中的功能，我们提出证据表明，p300 的 S106 被 ATM 磷酸化，调节 NBS1 的稳定性和募集到受损 DNA 中，可能导致 DNA 修复的调节。不可磷酸化的 p300（S106A）使 NBS1 不稳定，并减少 NBS1-p300 相互作用。在存在 S106A 的情况下，NBS1 募集到受损 DNA 受到损害。此外，缺乏酶活性的显性负 p300 诱导 NBS1 不稳定，表明其乙酰转移酶对于 NBS1 的稳定性是必需的。这些结果表明，p300 的磷酸化可以调节 NBS1 介导的 DNA 损伤反应，并且这些事件以乙酰化依赖性的方式发生。
