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酿酒酵母DNA聚合酶η转录本与蛋白质的调控

Regulation of Saccharomyces cerevisiae DNA polymerase eta transcript and protein.

作者信息

Pabla Ritu, Rozario Donald, Siede Wolfram

机构信息

Department of Cell Biology and Genetics, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, USA.

出版信息

Radiat Environ Biophys. 2008 Feb;47(1):157-68. doi: 10.1007/s00411-007-0132-1. Epub 2007 Sep 14.

Abstract

RAD30-encoded DNA polymerase eta functions as a translesion polymerase that can bypass the most frequent types of UV-induced pyrimidine photoproducts in an error-free manner. Although its transcript is UV-inducible in Saccharomyces cerevisiae, Rad30 (studied as a Rad30-Myc fusion) is a stable protein whose levels do not fluctuate following UV treatment or during cell cycle progression. Rad30 protein is subject to monoubiquitination whose level is upregulated in G1 and downregulated during S-phase reentry. This downregulation is accelerated in UV-treated cells. A missense mutation (L577Q) of the ubiquitin binding domain (UBZ) confers a reduced degree of ubiquitination outside of G1 and a complete failure to stably interact with ubiquitinated substrates. This mutation confers a phenotype resembling a complete RAD30 deletion, thus attesting to the significance of the UBZ motif for polymerase eta function in vivo.

摘要

由RAD30编码的DNA聚合酶η作为一种跨损伤聚合酶,能够以无差错的方式绕过最常见的紫外线诱导的嘧啶光产物类型。尽管其转录本在酿酒酵母中是紫外线可诱导的,但Rad30(作为Rad30-Myc融合蛋白进行研究)是一种稳定的蛋白质,其水平在紫外线处理后或细胞周期进程中不会波动。Rad30蛋白会发生单泛素化,其水平在G1期上调,在重新进入S期时下调。在紫外线处理的细胞中,这种下调会加速。泛素结合结构域(UBZ)的一个错义突变(L577Q)导致在G1期之外泛素化程度降低,并且完全无法与泛素化底物稳定相互作用。这种突变赋予了一种类似于完全缺失RAD30的表型,从而证明了UBZ基序对于体内聚合酶η功能的重要性。

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