The BCL11A transcription factor stimulates the enzymatic activities of the OGG1 DNA glycosylase

IF 2.9 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Tetiana Petrachkova, Olha Soldatkina, Lam Leduy, Alain Nepveu
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引用次数: 0

Abstract

The BCL11A transcription factor has previously been shown to interact with and stimulate the enzymatic activities of the NTHL1 DNA glycosylase and Pol β polymerase. Here we show that BCL11A and a smaller peptide encompassing amino acids 160 to 520 can interact with the 8-oxoguanine DNA glycosylase, OGG1, increase the binding of OGG1 to DNA that contains an 8-oxoguanine base and stimulate the glycosylase activity of OGG1. Following BCL11A knockdown, we observed an increase in oxidized purines in the genome using comet assays, while immunoassays reveal an increase in 8-oxoG bases. Structure-function analysis indicates that the stimulation of OGG1 by BCL11A requires the zinc fingers 1, 2 and 3 as well as the proline-rich region between the first and second zing finger, but a glutamate-rich region downstream of zinc finger 3 is dispensable. Ectopic expression of a small peptide that contains the three zinc fingers can rescue the increase in 8-oxoguanine caused by BCL11A knockdown. These findings, together with previous results showing that BCL11A stimulates the enzymatic activities of NTHL1 and the Pol β polymerase, suggest that high expression of BCL11A is important to protect cancer cells against oxidative DNA damage.
BCL11A 转录因子刺激 OGG1 DNA 糖基化酶的酶活性
先前已证明 BCL11A 转录因子能与 NTHL1 DNA 糖基化酶和 Pol β 聚合酶相互作用并刺激其酶活性。在这里,我们发现 BCL11A 和一个包含 160 至 520 个氨基酸的小肽能与 8-氧代鸟嘌呤 DNA 糖基化酶 OGG1 相互作用,增加 OGG1 与含有 8-氧代鸟嘌呤碱基的 DNA 的结合,并刺激 OGG1 的糖基化酶活性。在敲除 BCL11A 后,我们利用彗星试验观察到基因组中氧化嘌呤的增加,而免疫测定则显示 8-oxoG 碱基的增加。结构-功能分析表明,BCL11A 对 OGG1 的刺激需要锌指 1、2 和 3 以及锌指 1 和锌指 2 之间的富脯氨酸区,但锌指 3 下游的富谷氨酸区则不需要。异位表达含有这三个锌指的小肽可以挽救因 BCL11A 基因敲除引起的 8-氧鸟嘌呤的增加。这些发现以及之前的研究结果表明,BCL11A能刺激NTHL1和Pol β聚合酶的酶活性,表明BCL11A的高表达对保护癌细胞免受氧化性DNA损伤非常重要。
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来源期刊
Biological Chemistry
Biological Chemistry 生物-生化与分子生物学
CiteScore
7.20
自引率
0.00%
发文量
63
审稿时长
4-8 weeks
期刊介绍: Biological Chemistry keeps you up-to-date with all new developments in the molecular life sciences. In addition to original research reports, authoritative reviews written by leading researchers in the field keep you informed about the latest advances in the molecular life sciences. Rapid, yet rigorous reviewing ensures fast access to recent research results of exceptional significance in the biological sciences. Papers are published in a "Just Accepted" format within approx.72 hours of acceptance.
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