在端粒中,TRF1和TRF2形成了不同的shelterin亚复合体
Tomáš Janovič1, Gloria I Perez1, Jens C Schmidt1,2
1Institute for Quantitative Health Science and Engineering, Gynecology and Reproductive Biology, Michigan State University, East Lansing.
bioRxiv : the preprint server for biology
|January 7, 2025
概括
对于端粒维护至关重要的shelterin复合体,形成了不同的子复合体. 这些子复合体TRF1-TIN2-TPP1-POT1和TRF2-RAP1在端粒中表现出不同的动态,影响DNA修复调节.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 遗传学 遗传学 是一个
背景情况:
- 谢尔特林复合体保护染色体末端,并调节端粒酶活性.
- 谢尔特林包括六种蛋白质 (TRF1,TRF2,TIN2,TPP1,POT1,RAP1),它们在体外形成子综合体.
- 尚不清楚shelterin在体内精确的固体测量和动态端粒关联.
研究的目的:
- 在活细胞中定量分析庇护体的功能和动态.
- 为了确定每个shelterin子单元的丰度和端粒拷贝数.
- 阐明shelterin蛋白与端粒的动态关联.
主要方法:
- 生成的癌细胞系与内源性表达的HaloTagged庇护蛋白.
- 每个shelterin子单元的量化总细胞丰度和端粒拷贝数.
- 利用单分子活细胞成像来分析端粒庇护蛋白的动态.
主要成果:
- 庇护蛋白质在端粒中以相同的数量存在.
- TRF1-TIN2-TPP1-POT1和TRF2-RAP1在非重叠的端粒染色体位点形成了不同的子组.
- TRF1-TIN2-TPP1-POT1表现出密切的染色体关联,而TRF2-RAP1显示出动态结合,促进了辅助因子的招募.
结论:
- 谢尔特林复杂的组成和动态对于端粒维护至关重要.
- 不同的子复合体在保护染色体末端时调解不同的功能.
- 这项研究提供了对端粒染色体结构和功能的机制性见解.
相关概念视频
Telomeres and Telomerase
23.0K
In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded...
23.0K
Replicative Cell Senescence
3.6K
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
3.6K
Replication in Eukaryotes
170.3K
Overview
170.3K
Restarting Stalled Replication Forks
5.7K
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,...
5.7K
Homologous Recombination
50.1K
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...
50.1K
Condensins
3.4K
Condensins are large protein complexes that use ATP to fuel the assembly of chromosomes during mitosis. They transform the tangled, shapeless mass of post-interphase DNA into individualized chromosomes by compacting, organizing, and segregating chromosomal DNA.
The plant and animal cells contain two types of condensin complexes—condensin I and condensin II. Both complexes have five subunits: two SMC (Structural Maintenance of Chromosomes) subunits, a kleisin subunit, and two HEAT-repeat...
The plant and animal cells contain two types of condensin complexes—condensin I and condensin II. Both complexes have five subunits: two SMC (Structural Maintenance of Chromosomes) subunits, a kleisin subunit, and two HEAT-repeat...
3.4K


