特拉贝克丁因破坏了转录合核酸切除修复,以诱导高度转录的基因中的DNA断裂
Kook Son1, Vakil Takhaveev2, Visesato Mor1
1Center for Genomic Integrity, Institute for Basic Science (IBS), 44919, Ulsan, Republic of Korea.
Nature communications
|February 15, 2024
概括
特拉贝克丁对具有活性DNA修复的癌细胞更有毒. 这项研究揭示了trabectedin在转录合核酸切除修复 (TC-NER) 过程中如何形成DNA断裂,从而推进其在精密瘤学中的应用.
科学领域:
- 分子生物学分子生物学
- 癌症治疗方法 癌症治疗方法
- 遗传学 遗传学 是一个
背景情况:
- 基因毒性抗癌剂在具有完整DNA修复机制的瘤中是无效的.
- 在具有活性DNA修复的细胞中,特别是转录合核酸切除修复 (TC-NER) 中,特拉贝克特丁表现出增强的毒性.
研究的目的:
- 阐明特拉贝克丁的TC-NER-依赖性毒性的机制.
- 为了指导特拉贝克丁在癌症治疗中的精确应用.
主要方法:
- 由trabectedin引起的单链断裂 (SSBs) 的全基因组映射.
- 对TC-NER通路与trabectedin-DNA adducts的接触进行分析.
主要成果:
- 通过阻断NER切口,trabectedin-DNA adducts的流产TC-NER导致持久的SSB.
- 特拉贝克丁诱导的SSB主要发生在活跃基因的转录链上,在转录开始地点附近.
- 在基因体外也观察到SSB,与异性转录有关.
结论:
- 这项研究澄清了trabectedin的作用机制,突出了它对TC-NER的依赖.
- 这些发现支持trabectedin在精密瘤学中的作用,用于治疗特定类型的瘤.
- 这项研究为研究TC-NER和转录动态提供了一个框架.
更多相关视频
06:59Using Next Generation Sequencing to Identify Mutations Associated with Repair of a CAS9-induced Double Strand Break Near the CD4 Promoter
Published on: March 31, 2022
2.4K
08:15gDNA Enrichment by a Transposase-based Technology for NGS Analysis of the Whole Sequence of BRCA1, BRCA2, and 9 Genes Involved in DNA Damage Repair
Published on: October 6, 2014
12.3K
相关概念视频
Nucleotide Excision Repair
3.5K
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
3.5K
Base Excision Repair
22.3K
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...
22.3K
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
DNA Damage can Stall the Cell Cycle
9.2K
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...
9.2K
DNA-only Transposons
14.5K
DNA-only transposons are called autonomous transposons since they code for the enzyme transposase that is required for the transposition mechanism. Insertion of transposons can alter gene functions in multiple ways. They can mutate the gene, alter gene expression by introducing a novel promoter or insulator sequence, introduce new splice sites, and change the mRNA transcripts produced, or remodel chromatin structure.
The donor site from where the transposon is excised is either degraded or...
The donor site from where the transposon is excised is either degraded or...
14.5K
Mutations
37.5K
Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
37.5K
