DNA Repair And Somatic Mutation In Antibody Variable Gen
抗体可变基因中的 DNA 修复和体细胞突变
基本信息
- 批准号:7325391
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
Somatic hypermutation of immunoglobulin genes occurs at a frequency that is a million times greater than mutation in other genes. Mutations are found in both variable genes and switch regions before constant genes. The molecular mechanism that introduces these mutations is intensely being studied. Hypermutation is initiated when the activation-induced cytidine deaminase (AID) protein deaminates cytosine in DNA to uracil, which causes C:G mutations. However, in B lymphocytes, substitutions of all four bases occur at similar levels, indicating that other proteins are required to generate mutations of A:T base pairs. We are studying how DNA polymerases are involved in the process. Polymerase eta is clearly involved in the process by causing substitutions of A:T basepairs, whereas polymerase iota has a controversial role. To examine polymerase iota in a genetically defined background, we backcrossed the 129 nonsense mutation to the C57BL/6 strain for six generations. Class switch recombination and hypermutation were studied in these mice and in congenic mice doubly deficient for both polymerases eta and iota. The absence of both polymerases did not affect production of IgG1, indicating that these enzymes are not involved in switch recombination. Poli-/-F6 mice had the same types of nucleotide substitutions in variable genes as their C57BL/6 counterparts, and mice doubly deficient for polymerases eta and iota had the same mutational spectrum as Polh-/- mice. Thus, polymerase iota did not contribute to the mutational spectra, even in the absence of polymerase eta.
免疫球蛋白基因的体细胞超突变发生的频率是其他基因突变的一百万倍。在恒定基因之前,在可变基因和开关区都发现了突变。引入这些突变的分子机制正在被深入研究。当激活诱导的胞苷脱氨酶(AID)蛋白将DNA中的胞嘧啶脱氨为尿嘧啶时,启动超突变,这导致C:G突变。然而,在B淋巴细胞中,所有四种碱基的取代都以相似的水平发生,表明需要其他蛋白质来产生A:T碱基对的突变。我们正在研究DNA聚合酶是如何参与这一过程的。聚合酶eta通过引起A:T碱基对的取代而明显参与该过程,而聚合酶iota具有有争议的作用。为了在遗传学定义的背景中检查聚合酶iota,我们将129无义突变与C57 BL/6菌株回交六代。在这些小鼠和聚合酶eta和iota双重缺陷的同类小鼠中研究了类别转换重组和超突变。这两种聚合酶的缺乏不影响IgG 1的产生,表明这些酶不参与开关重组。Poli-/-F6小鼠与C57 BL/6小鼠在可变基因中具有相同类型的核苷酸取代,聚合酶eta和iota双重缺陷的小鼠与Polh-/-小鼠具有相同的突变谱。因此,聚合酶iota没有贡献的突变谱,即使在聚合酶eta的情况下。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
PATRICIA J GEARHART其他文献
PATRICIA J GEARHART的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('PATRICIA J GEARHART', 18)}}的其他基金
DNA Repair And Somatic Mutation In Antibody Variable Genes
抗体可变基因中的 DNA 修复和体细胞突变
- 批准号:
7592044 - 财政年份:
- 资助金额:
-- - 项目类别:
相似海外基金
DNA repair pathway choice mediates somatic cell reprogramming
DNA修复途径选择介导体细胞重编程
- 批准号:
9973944 - 财政年份:2020
- 资助金额:
-- - 项目类别:
DNA repair pathway choice mediates somatic cell reprogramming
DNA修复途径选择介导体细胞重编程
- 批准号:
10618907 - 财政年份:2020
- 资助金额:
-- - 项目类别:
DNA repair pathway choice mediates somatic cell reprogramming
DNA修复途径选择介导体细胞重编程
- 批准号:
10413221 - 财政年份:2020
- 资助金额:
-- - 项目类别:
DNA repair pathway choice mediates somatic cell reprogramming
DNA修复途径选择介导体细胞重编程
- 批准号:
10249291 - 财政年份:2020
- 资助金额:
-- - 项目类别:
DNA Repair And Somatic Mutation In Antibody Variable Genes
抗体可变基因中的 DNA 修复和体细胞突变
- 批准号:
7592044 - 财政年份:
- 资助金额:
-- - 项目类别:
DNA REPAIR AND SOMATIC MUTATION IN ANTIBODY VARIABLE GENES
抗体可变基因中的 DNA 修复和体细胞突变
- 批准号:
6097872 - 财政年份:
- 资助金额:
-- - 项目类别:
DNA Repair And Somatic Mutation In Antibody Variable Gen
抗体可变基因中的 DNA 修复和体细胞突变
- 批准号:
6668746 - 财政年份:
- 资助金额:
-- - 项目类别:
DNA Repair And Somatic Mutation In Antibody Variable Gen
抗体可变基因中的 DNA 修复和体细胞突变
- 批准号:
6969397 - 财政年份:
- 资助金额:
-- - 项目类别:
DNA Repair And Somatic Mutation In Antibody Variable Gen
抗体可变基因中的 DNA 修复和体细胞突变
- 批准号:
6969395 - 财政年份:
- 资助金额:
-- - 项目类别: