在增长和免疫球蛋白V (D) J重组中对Ku80的要求

A Nussenzweig1, C Chen, V da Costa Soares

  • 1Department of Medical Physics, Memorial Sloan-Kettering Cancer Centre, New York 10021, USA.

Nature
|August 8, 1996
PubMed

Insights

结合DNA的蛋白Ku80对于DNA修复和淋巴细胞中的V(D) J重组至关重要. Ku80 缺乏也会意外地影响哺乳动物的生长控制.

科学领域:

  • 分子生物学分子生物学
  • 免疫学 免疫学 免疫学
  • 遗传学 是一个遗传学.

背景情况:

  • 依赖DNA的蛋白激酶 (DNA-PK) 对于DNA修复,复制,转录和V(D) J重组至关重要.
  • DNA-PK的DNA结合子单元Ku80在这些过程中起着关键作用.

研究的目的:

  • 为了研究DNA-PK的Ku80亚单元的体内功能.
  • 阐明Ku80在淋巴细胞发育和DNA修复机制中的作用.

主要方法:

  • 在小鼠 (Ku80-/-) 中对Ku80的向基因淘汰.
  • 在突变小鼠中分析淋巴细胞发育和V(D) J重组.
  • 在Ku80-/-纤维细胞中评估细胞增殖,倍增时间和细胞周期检查点.

主要成果:

  • 库80缺乏导致T和B淋巴细胞发育停止,并导致V(D) J重组受损.
  • Ku80-/-小鼠表现出显著的生长缺陷,比对照小40-60%.
  • 来自Ku80-/-胚胎的纤维细胞显示出减少的增殖,更长的翻倍时间和完整的细胞周期检查点.

结论:

  • Ku80对于正常的淋巴细胞发育和V(D) J重组至关重要.
  • 该研究揭示了Ku80在哺乳动物生长控制中的意想不到的作用.
  • Ku80的功能超出了DNA修复的范围,影响细胞增殖和整个生物体的生长.
抽象的

No abstract available in PubMed .

相关概念视频

Viral Recombination00:57

Viral Recombination

Cells are sometimes infected by more than one virus at once. When two viruses disassemble to expose their genomes for replication in the same cell, similar regions of their genomes can pair together and exchange sequences in a process called recombination. Alternatively, viruses with segmented genomes can swap segments in a process called reassortment.
Homologous Recombination02:31

Homologous Recombination

The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
Conservative Site-specific Recombination and Phase Variation02:53

Conservative Site-specific Recombination and Phase Variation

Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
Exon Recombination02:32

Exon Recombination

The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes. 
Exon shuffling follows “splice frame rules.” Each exon has three reading...
Homologous Recombination02:31

Homologous Recombination

The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
Diversity of Antigen Receptors01:28

Diversity of Antigen Receptors

Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...