Dabin Juliette, Fortuny Anna, Polo Sophie E
Epigenome Integrity Group, UMR 7216 CNRS, Paris Diderot University, Sorbonne Paris Cité, 75013 Paris Cedex 13, France.
Epigenome Integrity Group, UMR 7216 CNRS, Paris Diderot University, Sorbonne Paris Cité, 75013 Paris Cedex 13, France.
Mol Cell. 2016 Jun 2;62(5):712-27. doi: 10.1016/j.molcel.2016.04.006.
Organism viability relies on the stable maintenance of specific chromatin landscapes, established during development, that shape cell functions and identities by driving distinct gene expression programs. Yet epigenome maintenance is challenged during transcription, replication, and repair of DNA damage, all of which elicit dynamic changes in chromatin organization. Here, we review recent advances that have shed light on the specialized mechanisms contributing to the restoration of epigenome structure and function after DNA damage in the mammalian cell nucleus. By drawing a parallel with epigenome maintenance during replication, we explore emerging concepts and highlight open issues in this rapidly growing field. In particular, we present our current knowledge of molecular players that support the coordinated maintenance of genome and epigenome integrity in response to DNA damage, and we highlight how nuclear organization impacts genome stability. Finally, we discuss possible functional implications of epigenome plasticity in response to genotoxic stress.
生物体的生存能力依赖于在发育过程中建立的特定染色质景观的稳定维持，这些景观通过驱动不同的基因表达程序来塑造细胞功能和特性。然而，在DNA损伤的转录、复制和修复过程中，表观基因组的维持面临挑战，所有这些过程都会引发染色质组织的动态变化。在这里，我们回顾了最近的进展，这些进展揭示了有助于哺乳动物细胞核DNA损伤后表观基因组结构和功能恢复的特殊机制。通过将其与复制过程中的表观基因组维持进行类比，我们探索了新出现的概念，并突出了这个快速发展领域中尚未解决的问题。特别是，我们介绍了目前对支持基因组和表观基因组完整性协同维持以应对DNA损伤的分子参与者的认识，并强调了核组织如何影响基因组稳定性。最后，我们讨论了表观基因组可塑性对基因毒性应激反应可能产生的功能影响。
