Unidad de Investigación, Hospital Universitario de Canarias , La Laguna, Spain.
Instituto de Tecnologías Biomédicas, Universidad de La Laguna , Tenerife, Spain.
Cell Cycle. 2020 Sep;19(17):2083-2093. doi: 10.1080/15384101.2020.1796037. Epub 2020 Jul 30.
Chromatin plays a pivotal role in regulating the DNA damage response and during DNA double-strand break repair. Upon the generation of DNA breaks, the chromatin structure is altered by post-translational modifications of histones and chromatin remodeling. How the chromatin structure, and the epigenetic information that it carries, is reestablished after the completion of DNA break repair remains unclear though. Also, how these processes influence recovery of the cell cycle remains poorly understood. We recently performed a reverse genetic screen for novel chromatin regulators that control checkpoint recovery after DNA damage. Here we discuss the implications of PHD finger protein 6 (PHF6) and additional candidates from the NuA4 ATPase-dependent chromatin-remodeling complex and the Cohesin complex, required for sister chromatid cohesion, in DNA repair and checkpoint recovery in more detail. In addition, the potential role of this novel function of PHF6 in cancer development and treatment is reviewed.
染色质在调节 DNA 损伤反应和 DNA 双链断裂修复中起着关键作用。在 DNA 断裂产生后,通过组蛋白的翻译后修饰和染色质重塑来改变染色质结构。然而,在 DNA 断裂修复完成后,染色质结构以及其所携带的表观遗传信息如何重新建立仍然不清楚。此外,这些过程如何影响细胞周期的恢复也知之甚少。我们最近进行了一项反向遗传筛选,以寻找控制 DNA 损伤后检查点恢复的新型染色质调节因子。在这里,我们更详细地讨论了 PHD 手指蛋白 6(PHF6)以及 NuA4 ATP 依赖性染色质重塑复合物和姐妹染色单体黏合所必需的 Cohesin 复合物中的其他候选物在 DNA 修复和检查点恢复中的意义。此外,还回顾了 PHF6 的这一新型功能在癌症发生和治疗中的潜在作用。