Disruption of mouse XAB2 gene involved in pre-mRNA splicing, transcription and transcription-coupled DNA repair results in preimplantation lethality
Disruption of mouse XAB2 gene involved in pre-mRNA splicing, transcription and transcription-coupled DNA repair results in preimplantation lethality
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DOI：
10.1016/j.dnarep.2004.12.004
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发表时间：
2005-04-04
期刊：
影响因子：
3.8
通讯作者：
Tanaka, K
中科院分区：
文献类型：
--
作者：
Yonemasu, R;Minami, M;Tanaka, K
具有 15 个四肽重复基序的 XAB2 蛋白（XPA 结合蛋白 2）因其与酵母双杂交系统中着色性干皮病 A 组 (XPA) 蛋白相互作用的能力而被分离出来。研究表明，XAB2 与 Cockayne 综合征 A 组和 B 组（CSA 和 CSB）蛋白以及 RNA 聚合酶 H 相互作用，已知这些蛋白参与转录偶联修复（TCR）和转录，并且抗 XAB2 蛋白的抗体在显微注射到活成纤维细胞中时，会抑制 UV 照射后 RNA 合成的恢复和正常 RNA 合成。这些结果表明XAB2参与TCR和转录。在本报告中，为了阐明 XAB2 的体内功能，在小鼠的 XAB2 基因中引入了两种类型的突变：启动子和外显子 1-4 区域的缺失，以及 C 端 162 个氨基酸的缺失。两种类型的 XAB2 杂合子小鼠在生理和行为上均表现正常。然而，XAB2纯合子在新生小鼠中选择性缺失。对不同发育阶段胚胎的详细分析表明，XAB2纯合突变体可以存活到桑葚胚阶段，但不能发育到囊胚阶段。这些结果表明 XAB2 在小鼠胚胎发生中具有重要功能。 (c) 2004 Elsevier B.V. 保留所有权利。
The XAB2 protein (XPA-binding protein 2) with 15 tetratricopeptide repeat motifs has been isolated by virtue of its ability to interact with xeroderma pigmentosum group A (XPA) protein in the yeast two-hybrid system. It has been shown that XAB2 interacted with Cockayne syndrome groups A and B (CSA and CSB) proteins and RNA polymerase H, which are known to be involved in transcription-coupled repair (TCR) and transcription, and that the antibodies against XAB2 protein inhibited the recovery of RNA synthesis after UV irradiation and normal RNA synthesis when microinjected into living fibroblasts. These results have indicated that XAB2 is involved in TCR and transcription. In this report, to elucidate the function of XAB2 in vivo, two types of mutations were introduced into the XAB2 gene in mice: a deletion of the region encompassing the promoter and exons 1-4, and a deletion of the C-terminal 162 amino acids. Both types of XAB2-heterozygous mice appeared normal physiologically and behaviorally. However, XAB2-homozygotes were selectively absent among the newborn mice. A detailed analysis of embryos at different stages of development indicated that the XAB2-homozygous mutants could survive until the morula stage, but could not develop to the blastocyst stage. These results indicate that XAB2 has an essential function in mouse embryogenesis. (c) 2004 Elsevier B.V. All rights reserved.