DNA POLYMERASE ETA/DNA/DNTP COCRYSTALS: A LARGE UNIT CELL PROBLEM

DNA 聚合酶 ETA/DNA/DNTP 共晶体：大单位细胞问题

• 批准号: 8170627
• 负责人: ANEEL K. AGGARWAL
• 金额: $ 0.27万
• 依托单位: BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8170627
• 关键词: Adenine; Area; Bypass; Cells; Computer Retrieval of Information on Scientific Projects Database; DNA; DNA Repair Pathway; DNA biosynthesis; DNA-Directed DNA Polymerase; Disease; Family; Funding; Grant; Human; Inherited; Institution; Lesion; Malignant Neoplasms; Mutagenesis; Mutation; Organism; Polymerase; Rad30 protein; Research; Research Personnel; Resources; Source; Thymine Dimers; Tumor Suppressor Proteins; UV induced; United States National Institutes of Health; Variant; Xeroderma Pigmentosum; carcinogenesis; dimer; prototype; repaired

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The survival of all organisms depends critically on the ability to faithfully replicate DNA. Cellular DNA is continually subjected to damaging agents and a variety of DNA repair pathways have evolved to repair the resulting lesions. How cells bypass these lesions during DNA replication has been a key question in the areas of DNA replication, mutagenesis, and carcinogenesis. The answer to this longstanding puzzle came only recently with the discovery of DNA polymerase eta (Pol eta), a prototype of a new family of translesion DNA synthesis (TLS) polymerases. Pol eta is unique amongst eukaryotic DNA polymerases in its proficient ability to replicate through a UV-induced cis-syn cyclobutane thymine-thymine (T-T) dimer by inserting two adenines opposite the dimer. Mutations in human Pol eta are responsible for an inherited cancer-prone disorder, the variant form of xeroderma pigmentosum (XP-V). Pol eta is, thus, the first DNA polymerase demonstrated to act as a tumor suppressor in humans.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 中心，不一定是研究者的机构。 所有生物体的生存关键取决于忠实复制 DNA 的能力。 细胞 DNA 不断受到损伤剂的影响，并且已经进化出多种 DNA 修复途径来修复由此产生的损伤。 DNA复制过程中细胞如何绕过这些损伤一直是DNA复制、突变和致癌领域的一个关键问题。 随着 DNA 聚合酶 eta (Pol eta) 的发现，这个长期存在的难题的答案才得以解答，DNA 聚合酶 eta 是跨损伤 DNA 合成 (TLS) 聚合酶新家族的原型。 Pol eta 在真核 DNA 聚合酶中是独一无二的，因为它能够通过紫外线诱导的顺式-顺式环丁烷胸腺嘧啶-胸腺嘧啶 (T-T) 二聚体进行复制，方法是在二聚体对面插入两个腺嘌呤。 人类 Pol eta 的突变导致了一种遗传性癌症倾向疾病，即着色性干皮病 (XP-V) 的变异形式。 因此，Poleta 是第一个被证明可以作为人类肿瘤抑制因子的 DNA 聚合酶。