PARP1 基因敲除抑制 DNA 碱基切除修复基因的表达。

PARP1 Gene Knockout Suppresses Expression of DNA Base Excision Repair Genes.

机构信息

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia.

Federal Research Centre Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia.

出版信息

Dokl Biochem Biophys. 2023 Feb;508(1):6-11. doi: 10.1134/S1607672922700028. Epub 2023 Jan 18.

DOI:10.1134/S1607672922700028

PMID:36653586

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10042944/

Abstract

The effect of PARP1 knockout in HEK293 cells on the gene expression of DNA base excision repair (BER) proteins was studied. It was shown that the expression of all differentially expressed genes (DEGs) of BER was reduced by knockout. The expression of the DNA glycosylase gene NEIL1, which is considered to be one of the common "hubs" for binding BER proteins, has changed the most. The expression of genes of auxiliary subunits of DNA polymerases δ and ε is also significantly reduced. The PARP1 gene knockout cell line obtained is an adequate cell model for studying the activity of the BER process in the absence of PARP1 and testing drugs aimed at inhibiting repair processes. It has been found for the first time that knockout of the PARP1 gene results in a significant change in the level of expression of proteins responsible for ribosome biogenesis and the functioning of the proteasome.

摘要

研究了 PARP1 基因敲除对 HEK293 细胞中 DNA 碱基切除修复 (BER) 蛋白基因表达的影响。结果表明，所有差异表达基因 (DEGs) 的表达均因敲除而降低。被认为是结合 BER 蛋白的共同“枢纽”之一的 DNA 糖苷酶基因 NEIL1 的表达变化最大。DNA 聚合酶 δ 和 ε 的辅助亚基基因的表达也显著降低。获得的 PARP1 基因敲除细胞系是研究缺乏 PARP1 时 BER 过程活性和测试旨在抑制修复过程的药物的合适细胞模型。首次发现 PARP1 基因敲除导致核糖体生物发生和蛋白酶体功能的负责蛋白的表达水平显著变化。