D型环林与多个蛋白激酶以及DNA复制和修复因子PCNA相关
1Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York 11724.
Cell
|October 30, 1992
概括
人类循环蛋白D1,一种与癌症相关的蛋白质,与CDK和PCNA等细胞循环蛋白形成复合体. 这表明它在DNA复制和修复中的作用,将瘤发生与细胞增殖机制联系起来.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 人类环素D1与各种繁殖性疾病有关.
- 循环素D1的精确生物化学功能在很大程度上仍未知.
- 了解环素D1的相互作用对于破译其在疾病中的作用至关重要.
研究的目的:
- 为了研究人类环素D1.1.的生物化学相互作用.
- 为了识别与双胞胎纤维细胞中与环林D1相关联的蛋白质.
- 阐明在细胞过程中环林D1复合物的功能意义.
主要方法:
- 同免疫沉测试以确定相互作用的蛋白质.
- 对由环D1和环D3.3形成的蛋白质复合物的分析.
- 识别相关的多,包括酶和PCNA.
主要成果:
- 环素D1与CDK2,CDK4和CDK5蛋白激酶形成复合体.
- 发现21kDa (p21) 和36kDa (PCNA) 的多与环素D1.1相关.
- 环D3还与蛋白质激酶,p21和PCNA有关.
- 有证据表明,四元复合物的形成涉及D环素,CDK,PCNA和p21.
结论:
- 环素D1和D3与多种细胞循环调节蛋白相关,包括CDK和PCNA.
- 这些发现表明,D环林,CDK,p21和PCNA之间存在一个四元复合体.
- 这项研究将一种与瘤发生相关的人类循环蛋白与DNA复制和修复因子联系起来.
相关概念视频
Long-patch Base Excision Repair
Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
Translesion DNA Polymerases
Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
DNA Damage can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
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...
Restarting Stalled Replication Forks
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart, a...
DNA Damage Can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...


