Sebastian Robin, Aladjem Mirit I, Oberdoerffer Philipp
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, United States.
Division of Cancer Biology, National Cancer Institute, NIH, Rockville, MD, United States.
Front Genet. 2021 Oct 21;12:746380. doi: 10.3389/fgene.2021.746380. eCollection 2021.
Almost 25 years ago, the phosphorylation of a chromatin component, histone H2AX, was discovered as an integral part of the DNA damage response in eukaryotes. Much has been learned since then about the control of DNA repair in the context of chromatin. Recent technical and computational advances in imaging, biophysics and deep sequencing have led to unprecedented insight into nuclear organization, highlighting the impact of three-dimensional (3D) chromatin structure and nuclear topology on DNA repair. In this review, we will describe how DNA repair processes have adjusted to and in many cases adopted these organizational features to ensure accurate lesion repair. We focus on new findings that highlight the importance of chromatin context, topologically associated domains, phase separation and DNA break mobility for the establishment of repair-conducive nuclear environments. Finally, we address the consequences of aberrant 3D genome maintenance for genome instability and disease.
大约25年前，染色质成分组蛋白H2AX的磷酸化被发现是真核生物DNA损伤反应的一个组成部分。从那时起，人们对染色质背景下DNA修复的控制有了很多了解。成像、生物物理学和深度测序方面最近的技术和计算进展，使人们对核组织有了前所未有的深入了解，突出了三维（3D）染色质结构和核拓扑结构对DNA修复的影响。在这篇综述中，我们将描述DNA修复过程是如何适应并在许多情况下采用这些组织特征以确保准确的损伤修复。我们关注的新发现突出了染色质背景、拓扑相关结构域、相分离和DNA断裂移动性对于建立有利于修复的核环境的重要性。最后，我们讨论异常的3D基因组维持对基因组不稳定性和疾病的影响。
