连接体组蛋白维持基因组稳定并驱动细胞衰老过程。

IF 3.3 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
George Miloshev, Penyo Ivanov, Bela Vasileva, Milena Georgieva
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引用次数: 0

摘要

衰老是所有生物固有的一系列过程。细胞衰老有14个一般标志,其中大多数发生在分子水平上。在细胞衰老过程中,通常观察到基因组活性调节的显著干扰。基因组正常功能的全面混乱和破坏也是众所周知的癌细胞的特权,人们认为这种基因组的不稳定性提供了衰老和癌症之间的直接联系。核DNA在染色质中的空间组织是基因活性微调和精细调控的基础,并在衰老过程中发生变化。因此,染色质是基因和环境相遇和相互作用的平台。不同的蛋白质因子、小分子和代谢物影响这种染色质组织,并通过它驱动细胞退化,最终导致衰老。因此,研究染色质结构组织和动力学对于理解生命,可能是衰老过程至关重要。DNA和组蛋白之间复杂的相互作用折叠、组织和适应染色质结构。在组蛋白中,连接组蛋白家族的作用逐渐显现。最近的数据指出,连接体组蛋白在高阶染色质组织中起着独特的作用,这反过来又在很大程度上影响了衰老。在这里,我们讨论了新出现的证据,这些证据表明连接蛋白的功能超出了它们在染色质结构中的传统作用,突出了它们在基因组稳定性、细胞衰老和癌症发展中的关键作用,从而使它们成为治疗干预的有希望的靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Linker Histones Maintain Genome Stability and Drive the Process of Cellular Ageing.

Ageing comprises a cascade of processes that are inherent in all living creatures. There are fourteen general hallmarks of cellular ageing, the majority of which occur at a molecular level. A significant disturbance in the regulation of genome activity is commonly observed during cellular ageing. Overall confusion and disruption in the proper functioning of the genome are also well-known prerogatives of cancerous cells, and it is believed that this genomic instability provides a direct link between aging and cancer. The spatial organization of nuclear DNA in chromatin is the foundation of the fine-tuning and refined regulation of gene activity, and it changes during ageing. Therefore, chromatin is the platform on which genes and the environment meet and interplay. Different protein factors, small molecules and metabolites affect this chromatin organization and, through it, drive cellular deterioration and, finally, ageing. Hence, studying chromatin structural organization and dynamics is crucial for understanding life, presumably the ageing process. The complex interplay among DNA and histone proteins folds, organizes, and adapts chromatin structure. Among histone proteins, the role of the family of linker histones comes to light. Recent data point out that linker histones play a unique role in higher-order chromatin organization, which, in turn, impacts ageing to a prominent degree. Here, we discuss emerging evidence that suggests linker histones have functions that extend beyond their traditional roles in chromatin architecture, highlighting their critical involvement in genome stability, cellular ageing, and cancer development, thereby establishing them as promising targets for therapeutic interventions.

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