Cancer Biology Division, National Centre for Cell Science, Ganeshkhind Road, Pune, Maharashtra 411007, India.
Department of Biotechnology, Savitribai Phule Pune University, Ganeshkhind Road, Pune, Maharashtra 411007, India.
Biochim Biophys Acta Gene Regul Mech. 2024 Sep;1867(3):195044. doi: 10.1016/j.bbagrm.2024.195044. Epub 2024 May 17.
Maintenance of genome integrity is a precise but tedious and complex job for the cell. Several post-translational modifications (PTMs) play vital roles in maintaining the genome integrity. Although ubiquitination is one of the most crucial PTMs, which regulates the localization and stability of the nonhistone proteins in various cellular and developmental processes, ubiquitination of the histones is a pivotal epigenetic event critically regulating chromatin architecture. In addition to genome integrity, importance of ubiquitination of core histones (H2A, H2A, H3, and H4) and linker histone (H1) have been reported in several cellular processes. However, the complex interplay of histone ubiquitination and other PTMs, as well as the intricate chromatin architecture and dynamics, pose a significant challenge to unravel how histone ubiquitination safeguards genome stability. Therefore, further studies are needed to elucidate the interactions between histone ubiquitination and other PTMs, and their role in preserving genome integrity. Here, we review all types of histone ubiquitinations known till date in maintaining genomic integrity during transcription, replication, cell cycle, and DNA damage response processes. In addition, we have also discussed the role of histone ubiquitination in regulating other histone PTMs emphasizing methylation and acetylation as well as their potential implications in chromatin architecture. Further, we have also discussed the involvement of deubiquitination enzymes (DUBs) in controlling histone ubiquitination in modulating cellular processes.
维持基因组完整性对于细胞来说是一项精确但繁琐和复杂的工作。几种翻译后修饰（PTMs）在维持基因组完整性方面起着至关重要的作用。虽然泛素化是最重要的 PTM 之一，它调节非组蛋白在各种细胞和发育过程中的定位和稳定性，但组蛋白的泛素化是一个关键的表观遗传事件，可严格调节染色质结构。除了基因组完整性外，核心组蛋白（H2A、H2B、H3 和 H4）和连接组蛋白（H1）的泛素化在几种细胞过程中的重要性也有报道。然而，组蛋白泛素化与其他 PTM 之间的复杂相互作用，以及复杂的染色质结构和动力学，给阐明组蛋白泛素化如何保护基因组稳定性带来了重大挑战。因此，需要进一步的研究来阐明组蛋白泛素化与其他 PTMs 之间的相互作用及其在维持基因组完整性中的作用。在这里，我们综述了迄今为止已知的所有类型的组蛋白泛素化在转录、复制、细胞周期和 DNA 损伤反应过程中维持基因组完整性的作用。此外，我们还讨论了组蛋白泛素化在调节其他组蛋白 PTMs 中的作用，强调了甲基化和乙酰化以及它们在染色质结构中的潜在影响。此外，我们还讨论了去泛素化酶（DUBs）在控制组蛋白泛素化以调节细胞过程中的作用。
