Epigenetics & Cell Fate Centre, UMR7216 CNRS, Université de Paris, 75013 Paris, France.
Cells. 2020 Nov 5;9(11):2424. doi: 10.3390/cells9112424.
Chromatin integrity is key for cell homeostasis and for preventing pathological development. Alterations in core chromatin components, histone proteins, recently came into the spotlight through the discovery of their driving role in cancer. Building on these findings, in this review, we discuss how histone variants and their associated chaperones safeguard genome stability and protect against tumorigenesis. Accumulating evidence supports the contribution of histone variants and their chaperones to the maintenance of chromosomal integrity and to various steps of the DNA damage response, including damaged chromatin dynamics, DNA damage repair, and damage-dependent transcription regulation. We present our current knowledge on these topics and review recent advances in deciphering how alterations in histone variant sequence, expression, and deposition into chromatin fuel oncogenic transformation by impacting cell proliferation and cell fate transitions. We also highlight open questions and upcoming challenges in this rapidly growing field.
染色质完整性是细胞内稳态和预防病理性发展的关键。核心染色质成分（组蛋白）的改变最近通过发现其在癌症中的驱动作用而成为焦点。在此基础上，在这篇综述中，我们讨论了组蛋白变体及其相关伴侣如何保护基因组稳定性并预防肿瘤发生。越来越多的证据支持组蛋白变体及其伴侣在维持染色体完整性和 DNA 损伤反应的各个步骤中的作用，包括受损染色质动力学、DNA 损伤修复以及依赖损伤的转录调控。我们介绍了我们在这些主题上的现有知识，并回顾了最近在阐明组蛋白变体序列、表达和沉积到染色质中的改变如何通过影响细胞增殖和细胞命运转变来促进致癌转化方面的进展。我们还强调了这个快速发展领域中的悬而未决的问题和即将面临的挑战。
