Hepatitis B virus X protein impedes the DNA repair via itsassociation with trans

StephenW

http://7thspace.com/headlines/374712/hepatitis_b_virus_x_protein_impedes_the_dna_repair_via_itsassociation_with_transcription_factor_tfiih.html
Hepatitis B virus (HBV) infections play an important role in the development of hepatocellular carcinoma (HCC). HBV X protein (HBx) is a multifunctional protein that can modulate various cellular processes and plays a crucial role in the pathogenesis of HCC.

HBx is known to interact with DNA helicase components of TFIIH, a basal transcriptional factor and an integral component of DNA excision repair.

Results: In this study, the functional relevance of this association was further investigated in the context to DNA repair. By site-directed mutagenesis HBx's critical residues for interaction with TFIIH were identified.

Similarly, TFIIH mutants lacking ATPase domain and the conserved carboxyl-terminal domain failed to interact with HBx. Yeast and mammalian cells expressing HBxwt conferred hypersensitivity to UV irradiation, which is interpreted as a basic deficiency in nucleotide excision repair.

  HBxmut120 (Glu to Val) was defective in binding to TFIIH and failed to respond to UV.

Conclusions: We conclude that HBx may act as the promoting factor by inhibiting DNA repair causing DNA damage and accumulation of errors, thereby contributing to HCC development.

Author: Ishtiaq QadriKaneez FatimaHany Hafiz
Credits/Source: BMC Microbiology 2011, 11:48

StephenW

乙型肝炎病毒（HBV）感染中发挥肝细胞癌（HCC）的发展具有重要作用。乙肝病毒X蛋白（HBx蛋白）是一种多功能蛋白，可以调节不同的细胞过程，起着在肝癌发病机制中的关键作用。

HBx蛋白是众所周知的互动与TFIIH，一个基础转录因子与DNA切除修复的DNA解旋酶的重要组成部分组件。

结果：在这项研究中，这个协会的功能的相关性，进一步考察了DNA的修复情况。通过交流与TFIIH定点突变HBx蛋白的关键残基被发现。

同样，TFIIH缺乏ATP酶结构域的突变体和守恒羧基末端结构域与HBx蛋白相互作用失败。酵母和哺乳动物细胞表达HBxwt赋予过敏紫外线照射，这是作为一个基本的核苷酸切除修复缺陷解释。

HBxmut120（谷氨酸对缬氨酸）是欠妥的结合TFIIH，未能回应紫外线。

结论：我们认为，HBx蛋白可作为通过抑制DNA造成DNA损伤和修复的错误积累促进因子，从而促进肝癌的发展。

作者：Ishtiaq QadriKaneez FatimaHany哈菲兹
学分/资料来源：2011年的BMC微生物学，11:48