Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Department of Chromatin Structure and Functions, Vavilov Str. 32, Moscow 119991, Russia.
FEBS Lett. 2013 Sep 17;587(18):3108-14. doi: 10.1016/j.febslet.2013.08.007. Epub 2013 Aug 13.
The 26S proteasome is an ATP-dependent multi-subunit protease complex and the major regulator of intracellular protein turnover and quality control. However, its role in the DNA damage response is controversial. We addressed this question in yeast by disrupting the transcriptional regulation of the PRE1 proteasomal gene. The mutant strain has decreased proteasome activity and is hyper-resistant to various DNA-damaging agents. We found that Rpn4-target genes MAG1, RAD23, and RAD52 are overexpressed in this strain due to Rpn4 stabilisation. These genes represent three different pathways of base excision, nucleotide excision and double strand break repair by homologous recombination (DSB-HR). Consistently, the proteasome mutant displays increased DSB-HR activity. Our data imply that the proteasome may have a negative role in DNA damage response.
26S 蛋白酶体是一种依赖于 ATP 的多亚基蛋白酶复合物，是细胞内蛋白质周转和质量控制的主要调节剂。然而，其在 DNA 损伤反应中的作用存在争议。我们通过破坏 PRE1 蛋白酶体基因的转录调控在酵母中解决了这个问题。突变株的蛋白酶体活性降低，对各种 DNA 损伤剂具有超抗性。我们发现，由于 Rpn4 的稳定，该菌株中 Rpn4 靶向基因 MAG1、RAD23 和 RAD52 过表达。这些基因代表碱基切除、核苷酸切除和同源重组（DSB-HR）修复的三种不同途径。一致地，蛋白酶体突变体显示出增加的 DSB-HR 活性。我们的数据表明蛋白酶体可能在 DNA 损伤反应中起负作用。
