相关实验视频

Updated: Jul 13, 2025

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors

Published on: August 5, 2022

癌症DNA突变酶APOBEC3A的结构引导抑制

Stefan Harjes¹, Harikrishnan M Kurup¹, Amanda E Rieffer²

¹School of Natural Sciences, Massey University, Palmerston North, New Zealand.

Nature communications

|October 11, 2023

概括

研究人员发现了新型抑制剂,可以阻止APOBEC3A,一种导致癌症突变的酶. 这些化合物通过防止瘤进化和耐药性,显示出作为抗癌剂的潜力.

科学领域:

生物化学生物化学
分子生物学分子生物学
癌症研究癌症研究

背景情况:

APOBEC3A是一种酶,在人类癌症中充当内源性突变原体.
它的DNAC-to-U编辑活动导致突变,DNA破裂和染色体异常.
抑制APOBEC3A可以通过阻断突变发生和瘤进化性来提供一种新的抗癌策略.

研究的目的:

通过修改的DNA毛结构来阐明APOBEC3A抑制的结构基础.
了解APOBEC3A对YTCD图案的基质偏好的分子基础.
评估新型APOBEC3A抑制剂的功效和细胞活性.

主要方法:

使用X射线晶体学来确定APOBEC3A与DNA抑制剂复合的结构.
进行了生物化学测试,以评估合成化合物的抑制功效.
基于细胞的测试被用于确认人类细胞中APOBEC3A活性的抑制.

主要成果:

这项研究揭示了由含有2'-脱氧-5-祖氨酸的头DNA抑制APOBEC3A的竞争性抑制的结构机制.
阐明了APOBEC3A偏好YTCD动机的结构基础.
抑制剂的耐核酶酸衍生物在体外显示出纳米分子效能,并有效地阻断了细胞中的APOBEC3A活性.

结论:

开发了针对APOBEC3A的基于DNA的新型抑制剂.
这些抑制剂为APOBEC3A功能和抑制提供了结构性的洞察力.
这些抑制剂显示出作为研究工具和下一代抗癌疗法的潜在辅助剂的前景.

更多相关视频

Probing The Structure And Dynamics Of Nucleosomes Using Atomic Force Microscopy Imaging

Probing The Structure And Dynamics Of Nucleosomes Using Atomic Force Microscopy Imaging

Published on: January 31, 2019

Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors

Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors

Published on: February 28, 2021

相关概念视频

Targeted Cancer Therapies

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...

DNA Damage can Stall the Cell Cycle

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...

Inhibition of Cdk Activity

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...

Abnormal Proliferation

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...

The Intrinsic Apoptotic Pathway

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...

Base Excision Repair

Base Excision Repair

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...