GENE SPECIFIC DNA REPAIR

基因特异性 DNA 修复

• 批准号: 2565748
• 负责人: V 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/2565748
• 关键词: DNA damage; DNA repair; cell growth regulation; genetic regulation; genetic transcription; hamsters; human tissue; ultraviolet radiation

A. Studies have been done to clarify the relationship between cell cycle regulation and DNA repair in hamster cells: 1) UV irradiation of G1-synchronized cells causes a dose-dependent, p53-independent delay of entry into S phase. UV irradiation of G2-synchronized cells also causes a dose- and time-dependent delay before passage into the subsequent G1 phase. 2) Repair of cyclobutane pyrimidine dimers occurs with identical compartmentalization and equal efficiency during G1 and G2 phases. 3) An extended late S/G2 arrest observed after S phase UV irradiation results in apoptosis. 4) Delays in completion of replication, extended G2 arrest, and apoptosis were caused by the persistence of UV-induced DNA damage. 5) UV-induced 6-4 photoproducts are a much greater hindrance to replication than pyrimidine dimers. 6) Transcription of ERCC1, a gene involved in DNA repair and recombination, is elevated in late S and G2 phases in comparison to other periods of the cell cycle. Other repair genes studied (XPB, XPD, and CS-B) appear to be expressed at the same level throughout the cell cycle. B. Preferential, gene specific DNA repair occurs at the nuclear matrix, where transcription also is maximal. There is no coupling between transcription and repair in ribosomal DNA. C. In resting human CD4 lymphocytes, there is little or no repair in the essential gene DHFR. In proliferating lymphocytes we find both transcription associated gene specific repair increases and gene specific repair of genes that are not transcribed. The latter result suggests a connection between repair efficiency and the replicative status of the cell or DNA region. D. The repair of an episomal extra chromosomal gene is less efficient than repair of an endogenous gene.

答：已经进行了一些研究，以澄清细胞周期之间的关系 金黄地鼠细胞的调控和DNA修复：1)紫外线照射 G1同步化的细胞导致剂量依赖、P53无关的延迟 进入S阶段。紫外线照射G2同步化细胞也会导致 在进入下一个G1之前与剂量和时间有关的延迟 相位。2)环丁烷嘧啶二聚体的修复 在G1和G2阶段实行分区化和同等效率。3) 经S相紫外线照射后出现延长的晚期S/G2细胞停滞 会导致细胞凋亡。4)复制完成延迟，扩展的G2 紫外线诱导的DNA持续存在引起细胞停滞和细胞凋亡 损坏。5)紫外线诱导的6-4感光产物是一个更大的障碍 比嘧啶二聚体更容易复制。6)ERCC1基因转录 参与DNA修复和重组，在S和G2晚期升高 与细胞周期的其他时期相比，细胞周期的各个阶段。其他维修 所研究的基因(XPB、XPD和CS-B)似乎在同一时间表达 在整个细胞周期中的水平。 B.优先的，基因特异的DNA修复发生在核基质上， 其中转录也是最大的。它们之间没有耦合 核糖体DNA的转录和修复。 C.在静息的人类CD4淋巴细胞中，很少或没有修复 必需基因dhfr。在增殖的淋巴细胞中，我们发现两者都 转录相关基因特异性修复增加和基因特异性 修复未转录的基因。后一种结果表明 修复效率与细胞复制状态之间的关系 或DNA区域。 D.修复上体额外染色体基因的效率低于 修复内源基因的修复