A CONNECTION BETWEEN DNA REPAIR AND HIV RELATED IMMUNODEFICIENCY

DNA 修复与 HIV 相关免疫缺陷之间的联系

• 批准号: 6097874
• 负责人: VILHELM A. BOHR
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6097874
• 关键词: DNA directed DNA polymerase; DNA repair; HeLa cells; SCID mouse; T lymphocyte; calmodulin dependent protein kinase; enzyme inhibitors; fibroblasts; genetic transcription; human T cell lymphotropic virus type 1; human immunodeficiency virus 1; radiation genetics; recombinant DNA; transcription factor; ultraviolet radiation; virus genetics; virus protein

Summary of work: DNA repair enzymes are activated in response to DNA damage. Alterations in DNA repair enzyme function and thus the rate and extent of repair contribute to malignant transformation. Transcription of the gene encoding DNA polymerizing enzyme beta- polymerase, a repair enzyme, is shown to be inhibited by the human T-cell leukemia virus type I (HTLV-I) transactivator protein Tax. The resultant inhibition of DNA repair may lead to unrepaired chromosomal damage. Severe combined immunodeficient (SCID) mice have a mutation in the catalytic subunit of the DNA binding protein kinase that is involved in repair of double-strand breaks in DNA. To deter- mine if the protein is involved in repair of other types of breaks, we examined the ability of SCID cells to repair lesions introduced by ultraviolet light and X-ray irradiation. After ultraviolet irradiation, murine SCID fibroblast cell lines had 50% less repair of photoproducts in chromosomal DNA compared to a wildtype cell line, as shown by impaired cellular survival and decreased unscheduled DNA synthesis. SCID cells also had 50% less repair of ultraviolet damage in the transcribed dihydrofolate reductase and c-myc genes than wildtype cells. After gamma irradiation, SCID fibroblasts had 30% less repair of single-strand breaks than wildtype cells in the genes encoding immunoglobulin heavy and light chains.

工作总结：DNA修复酶是 DNA损伤后被激活DNA修复的改变 酶的功能，从而修复的速度和程度有助于 恶性转化编码DNA的基因的转录 聚合酶β-聚合酶，一种修复酶， 被人类T细胞白血病病毒I型（HTLV-I）抑制 反式激活蛋白Tax DNA修复的抑制作用 可能导致无法修复的染色体损伤严重联合 免疫缺陷（SCID）小鼠的催化基因突变， 参与修复的DNA结合蛋白激酶的亚基 DNA双链断裂为了确定蛋白质是否 参与修复其他类型的骨折，我们检查了这种能力， 的SCID细胞来修复紫外线引起的损伤， X射线照射。紫外线照射后，小鼠SCID 成纤维细胞系的光产物修复减少了50%， 与野生型细胞系相比，染色体DNA，如 受损的细胞存活和减少的非程序DNA 合成. SCID细胞对紫外线损伤的修复也减少了50% 在转录的二氢叶酸还原酶和c-myc基因中， 野生型细胞γ射线照射后，SCID成纤维细胞有30% 基因中单链断裂的修复比野生型细胞少 编码免疫球蛋白重链和轻链。