在3D人类基因组组织中,核酸切割修复阿弗拉托克辛诱导的DNA损伤
Yiran Wu1, Muhammad Muzammal Adeel1, Aziz Sancar2
1Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, GA 30602.
bioRxiv : the preprint server for biology
|October 9, 2023
概括
转录合修复显著消除了阿弗拉托xin B1 (AFB1) DNA 附加物,更快的修复发生在核内部和基因组组织结构周围. 这会影响肝癌的机制.
科学领域:
- 分子生物学分子生物学
- 基因组学就是基因组学.
- 毒理学 毒理学 毒理学
背景情况:
- 非洲毒素B1 (AFB1) 是一种强大的真菌毒素,也是肝癌的主要原因.
- AFB1生物激活导致DNA附带的形成,如果不修复,可能会导致突变.
研究的目的:
- 为了研究AFB1诱导的DNA adducts的核酸切除修复.
- 探索转录合修复在AFB1损伤消除中的作用.
- 分析3D基因组组织对AFB1DNA adduct修复的影响.
主要方法:
- 调整tXR-seq方法来量化AFB1DNA adduct修复.
- 消灭产品长度分布的分析.
- 研究3D基因组组织,包括核定位,A/B区,TAD边界和循环.
主要成果:
- 转录合修复是去除AFB1诱导的DNA添加物的主要途径.
- 切割产品呈现出明显的长度分布模式.
- 位于核中部和A区内的染色体更快地被修复.
- 在TAD边界和循环上观察到加速修复.
结论:
- 转录合修复和3D基因组组织显著影响AFB1DNA adducts的修复动态.
- 修复,转录和基因组架构之间的相互作用对于理解AFB1诱导的肝癌至关重要.
- 这些发现提供了关于AFB1.1驱动肝癌发生的分子机制的见解.
相关概念视频
Nucleotide Excision Repair
37.2K
Overview
37.2K
Base Excision Repair
22.4K
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...
22.4K
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
Overview of DNA Repair
31.1K
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...
31.1K
Homologous Recombination
50.6K
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...
50.6K
Base-pairing and DNA Repair
64.8K
64.8K


