Molecular genetic analysis of cellular response to transcription-blocking DNA damage and its defective disorders

细胞对转录阻断 DNA 损伤及其缺陷性疾病反应的分子遗传学分析

• 批准号: 17109006
• 负责人: TANAKA Kiyoji
• 金额: $ 72.63万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (S)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17109006/
• 关键词: 色素性乾皮症; コケイン症候群; DNA修復; 転写; 転写と共役した修復; ユビキチンリガーゼ; RNAポリメラーゼII; 微小核融合法; XPD; CGH array; ユビキチン化; ホルモン受容体; 色素性幹皮症; ユビキチン・リガーゼ; XPG; TFIIH; CAK; ホルモンレセプター; TFIIS; UV^s症候群; 酸化的DNA損傷; 微小核融合

Nucleotide excision repair (NER) is a versatile DNA repair system that removes a wide range of DNA lesions including UV-damage and oxidative DNA damage. The importance of NER is indicated by the study of xeroderma pigmentosum patients who show a high incidence of skin cancer and neurological abnormalities, and are deficient in NER. Transcription-blocking DNA damage in active genes is repaired by transcription-coupled NER (TCR). There are two autosomal recessive disorders that are specifically deficient in TCR : Cockayne syndrome (CS) and UV-sensitive syndrome (UV^sS). CS is characterized by photosensitivity and abnormal physical and neurological development. On the other hand, UV^sS patients show photosensitivity and mild freckling with no skin tumors. In this study, molecular mechanism of TCR and molecular pathogenesis of XP, CS and UV^sS have been analyzed.

核苷酸切除修复 (NER) 是一种多功能 DNA 修复系统，可消除多种 DNA 损伤，包括紫外线损伤和氧化性 DNA 损伤。对色素性干皮病患者的研究表明了 NER 的重要性，这些患者皮肤癌和神经系统异常的发病率很高，并且缺乏 NER。转录偶联 NER (TCR) 可修复活性基因中的转录阻断 DNA 损伤。有两种 TCR 特别缺乏的常染色体隐性遗传疾病：科凯恩综合征 (CS) 和紫外线敏感综合征 (UV^sS)。 CS 的特点是光敏性以及身体和神经发育异常。另一方面，UV^sS患者表现出光敏性和轻度雀斑，但没有皮肤肿瘤。本研究对TCR的分子机制以及XP、CS和UV^sS的分子发病机制进行了分析。

项目成果

Impaired spermatogenesis and elevated spontaneous tumorigenesis in xeroderma pigmentosum group A gene (Xpa)-deficient mice

着色性干皮病 A 组基因 (Xpa) 缺陷小鼠的精子发生受损和自发性肿瘤发生增加

• 发表时间: 2008
• 期刊: DNA Repair 7
• 作者: 小泉直人;山田宗慶;篠田謙一;Hironobu Nakane
• 通讯作者: Hironobu Nakane

RNA polymerase H bypasses 8-oxoguanine in the presence of transcription elongation factor TFIIS

在转录延伸因子 TFIIS 存在的情况下，RNA 聚合酶 H 绕过 8-氧代鸟嘌呤

• 发表时间: 2007
• 期刊: DNA Repair (印刷中)
• 作者: Kato;H.;Fukamizu;A.;Masafumi Saijo;篠田謙一;Isao Kuraoka
• 通讯作者: Isao Kuraoka

CSA-dependent degradation of CSB by ubiquitin-proteasome pathway establishes a link between complementation factors of the Cockayne syndrome.

泛素蛋白酶体途径对 CSB 的 CSA 依赖性降解在 Cockayne 综合征的互补因子之间建立了联系。

• 发表时间: 2006
• 期刊: Genes & Development 20
• 作者: Regina Groisman;Isao Kuraoka;Odile Chevallier;Nogaye Gaye;Thierry Magnaldo;Kiyoji Tanaka;Alexei F. Kisselev;Annik Harel-Bellan;Yoshihiro Nakatani
• 通讯作者: Yoshihiro Nakatani

CSA-dependent degradation of CSB by ubiquitin-proteasome pathway establishes a link between complementation factors of the Cockayne syndrome

泛素蛋白酶体途径对 CSB 的 CSA 依赖性降解建立了 Cockayne 综合征的互补因子之间的联系

• 发表时间: 2006
• 期刊: Genes ＆ Development 20
• 作者: G.K. Villena;L. Venkatesh;A. Yamazaki;S. Tsuyumu;M. Gutierrez-Correa;中橋 孝博;Regina Groisman
• 通讯作者: Regina Groisman

Mutation spectrum in UVB-exposed skin epidermis of Xpa-knockout mice:: Frequent recovery of triplet mutations

• DOI: 10.1002/em.20262
• 发表时间: 2007-01-01
• 期刊: ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
• 影响因子: 2.8
• 作者: Ikehata, Hironobu;Yanase, Fumitaka;Ono, Tetsuya
• 通讯作者: Ono, Tetsuya