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PRMT5对DNA修复基因表达的调控。

Regulation of DNA repair gene expression by PRMT5.

作者信息

Bliss Hunter, Bouley Renee A, Petreaca Ruben C

机构信息

Biology, The Ohio State University.

The Ohio State University.

出版信息

MicroPubl Biol. 2025 Jul 14;2025. doi: 10.17912/micropub.biology.001631. eCollection 2025.

Abstract

PRMT5 is a member of a class of enzymes called protein arginine methyltransferases (PRMTs) that play a role in maintaining genomic stability through post-translational modification of components of the TIP60 chromatin remodeling super complex. TIP60 is required primarily for chromatin remodeling at DNA double-strand breaks. Mutations in either TIP60 or PRMT5 affect repair by homologous recombination. A recent study has shown that in leukemia and lymphoma, PRMT5 also controls mRNA expression of TIP60 and other DNA repair genes by regulating alternative splicing. This analysis utilizes publicly available data from the Catalogue of Somatic Mutations in Cancer (COSMIC) to interrogate how PRMT5 expression correlates with expression levels of other key DNA repair genes: KAT5 (TIP60), H2A (H2AFX), TP53, TP53BP1, and RAD51 in all cancers. We find that indeed an increase in PRMT5 expression levels correlates with an increase in KAT5 levels. A weak correlation was also observed between PRMT5 and TP53, TP53BP1, and RAD51. These findings extend previous PRMT5 roles in controlling gene expression to all cancer types and further highlight the role of this enzyme not only in post-translational modification but also regulation of gene expression.

摘要

PRMT5是一类称为蛋白质精氨酸甲基转移酶(PRMTs)的酶的成员,这些酶通过对TIP60染色质重塑超复合物的组分进行翻译后修饰,在维持基因组稳定性中发挥作用。TIP60主要是DNA双链断裂处染色质重塑所必需的。TIP60或PRMT5中的突变会影响同源重组修复。最近的一项研究表明,在白血病和淋巴瘤中,PRMT5还通过调节可变剪接来控制TIP60和其他DNA修复基因的mRNA表达。该分析利用来自癌症体细胞突变目录(COSMIC)的公开数据,探讨PRMT5表达与所有癌症中其他关键DNA修复基因:KAT5(TIP60)、H2A(H2AFX)、TP53、TP53BP1和RAD51的表达水平如何相关。我们发现,PRMT5表达水平的增加确实与KAT5水平的增加相关。在PRMT5与TP53、TP53BP1和RAD51之间也观察到微弱的相关性。这些发现将PRMT5先前在控制基因表达方面的作用扩展到所有癌症类型,并进一步突出了这种酶不仅在翻译后修饰而且在基因表达调控中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ba4/12305363/dbc5d3ff4994/25789430-2025-micropub.biology.001631.jpg

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本文引用的文献

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