Tri-Institutional PhD Program in Chemical Biology, New York, NY, USA; Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Tri-Institutional PhD Program in Chemical Biology, New York, NY, USA; Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Pharmacology, Weill Cornell Medicine, New York, NY, USA; Department of Physiology, Biophysics, and Systems Biology, Weill Cornell Medicine, New York, NY, USA.
Trends Biochem Sci. 2021 Sep;46(9):718-730. doi: 10.1016/j.tibs.2021.04.004. Epub 2021 May 5.
The interior of the cell abounds with reactive species that can accumulate as non-enzymatic covalent modifications (NECMs) on biological macromolecules. These adducts interfere with many cellular processes, for example, by altering proteins' surface topology, enzymatic activity, or interactomes. Here, we discuss dynamic NECMs on chromatin, which serves as the cellular blueprint. We first outline the chemistry of NECM formation and then focus on the recently identified effects of their accumulation on chromatin structure and transcriptional output. We next describe the known cellular regulatory mechanisms that prevent or reverse NECM formation. Finally, we discuss recently developed chemical biology platforms for probing and manipulating these NECMs in vitro and in vivo.
细胞内部充满了反应性物质，这些物质可以在生物大分子上积累，形成非酶促共价修饰（NECM）。这些加合物会干扰许多细胞过程，例如通过改变蛋白质的表面拓扑结构、酶活性或互作组。在这里，我们讨论染色质上的动态 NECM，染色质是细胞的蓝图。我们首先概述 NECM 形成的化学原理，然后重点介绍其在染色质结构和转录产物积累方面的最新发现。接下来，我们描述了已知的细胞调控机制，这些机制可以防止或逆转 NECM 的形成。最后，我们讨论了最近开发的化学生物学平台，用于在体外和体内探测和操纵这些 NECM。
