REXO5通过使用其外核酶活性调节R循环来促进基因组完整性
Ye Jin Lee1, Seo Yun Lee2, Soomi Kim1
1Department of Biological Sciences, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
Leukemia
|July 30, 2024
概括
RNA外核酶5 (REXO5) 在R环内降解RNA,防止DNA损伤并支持正常细胞功能. 这一发现为慢性髓性白血病 (CML) 病原发生提供了新的见解.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 遗传学 遗传学 是一个
背景情况:
- 慢性髓性白血病 (CML) 的发病包括改变基因表达,但潜在的机制尚不清楚.
- BCR::ABL1融合基因通过调节基因表达来驱动CML的进展.
研究的目的:
- 为了确定参与CML病变的新型基因.
- 阐明REXO5在DNA损伤反应和CML中的分子机制.
主要方法:
- 使用了REXO5淘汰 (KO) K562细胞系和野生类型 (WT) 细胞.
- 通过其RNA识别动机 (RRM) 调查了REXO5转移到DNA损伤部位.
- 在REXO5KO细胞中评估了R循环积累,DNA损伤和ATR-CHK1激活.
主要成果:
- 在CML患者中,REXO5 mRNA表达升高.
- 与WT细胞相比,REXO5 KO细胞表现出增加的R环和DNA损伤.
- REXO5转移到DNA损伤部位,结合R环,并通过其外核酶域降解mRNA,调节R环水平和ATR-CHK1激活.
结论:
- 通过其外核酶活性,REXO5在R循环的生理控制中发挥着关键作用.
- 在R循环调节中的REXO5的功能为CML病原体提供了新的见解.
- REXO5的失调可能会导致CML的发展和进展.
更多相关视频
09:20Identification of RNA Fragments Resulting from Enzymatic Degradation using MALDI-TOF Mass Spectrometry
Published on: April 11, 2022
3.3K
07:55Detection of Homologous Recombination Intermediates via Proximity Ligation and Quantitative PCR in Saccharomyces cerevisiae
Published on: September 11, 2022
1.8K
相关概念视频
Nucleotide Excision Repair
37.0K
Overview
37.0K
Base Excision Repair
22.2K
One of the common DNA damages is the chemical alteration of single bases by alkylation, oxidation, or deamination. The altered bases cause mispairing and strand breakage during replication. This type of damage causes minimal change to the DNA double helix structure and can be repaired by the base excision repair (BER) pathways. BER corrects damaged DNA sequences by removing the damaged base and restoring the original base sequence using the complementary strand as a template.
The first step of...
The first step of...
22.2K
Homologous Recombination
50.4K
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...
50.4K
Long-patch Base Excision Repair
7.0K
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:
7.0K
Exon Recombination
3.6K
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...
Exon shuffling follows “splice frame rules.” Each exon...
3.6K
Overview of DNA Repair
30.9K
In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
Chemically...
30.9K
