Molecular dynamics of DNA repair and carcinogen interaction: Implications for cancer initiation, progression, and therapeutic strategies

IF 1.5 4区医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis Pub Date : 2024-07-01 DOI:10.1016/j.mrfmmm.2024.111883

Eman Alyafeai , Eskandar Qaed , Haitham Saad Al-mashriqi , Ahmed Almaamari , Anisa H. Almansory , Fatima Al Futini , Marwa Sultan , Zeyao Tang

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Abstract

The integrity of the genetic material in human cells is continuously challenged by environmental agents and endogenous stresses. Among these, environmental carcinogens are pivotal in initiating complex DNA lesions that can lead to malignant transformations if not properly repaired. This review synthesizes current knowledge on the molecular dynamics of DNA repair mechanisms and their interplay with various environmental carcinogens, providing a comprehensive overview of how these interactions contribute to cancer initiation and progression. We examine key DNA repair pathways including base excision repair, nucleotide excision repair, and double-strand break repair and their regulatory networks, highlighting how defects in these pathways can exacerbate carcinogen-induced damage. Further, we discuss how understanding these molecular interactions offers novel insights into potential therapeutic strategies. This includes leveraging synthetic lethality concepts and designing targeted therapies that exploit specific DNA repair vulnerabilities in cancer cells. By integrating recent advances in molecular biology, genetics, and oncology, this review aims to illuminate the complex landscape of DNA repair and carcinogen-induced carcinogenesis, setting the stage for future research and therapeutic innovations.

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DNA 修复与致癌物质相互作用的分子动力学：癌症发生、发展和治疗策略的意义

人类细胞中遗传物质的完整性不断受到环境因素和内源性压力的挑战。其中，环境致癌物质是引发复杂 DNA 病变的关键因素，如果修复不当，就会导致恶性转化。本综述综合了目前有关 DNA 修复机制的分子动力学及其与各种环境致癌物相互作用的知识，全面概述了这些相互作用如何导致癌症的发生和发展。我们研究了包括碱基切除修复、核苷酸切除修复和双链断裂修复在内的关键 DNA 修复途径及其调控网络，重点介绍了这些途径的缺陷如何加剧致癌物质诱发的损伤。此外，我们还讨论了了解这些分子相互作用如何为潜在的治疗策略提供新的见解。这包括利用合成致死概念和设计靶向疗法，利用癌细胞中特定的 DNA 修复漏洞。通过整合分子生物学、遗传学和肿瘤学的最新进展，本综述旨在阐明 DNA 修复和致癌物诱导的致癌过程的复杂情况，为未来的研究和治疗创新奠定基础。

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来源期刊

Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis 生物-毒理学

CiteScore

4.90

自引率

0.00%

发文量

审稿时长

51 days

期刊介绍： Mutation Research (MR) provides a platform for publishing all aspects of DNA mutations and epimutations, from basic evolutionary aspects to translational applications in genetic and epigenetic diagnostics and therapy. Mutations are defined as all possible alterations in DNA sequence and sequence organization, from point mutations to genome structural variation, chromosomal aberrations and aneuploidy. Epimutations are defined as alterations in the epigenome, i.e., changes in DNA methylation, histone modification and small regulatory RNAs. MR publishes articles in the following areas: Of special interest are basic mechanisms through which DNA damage and mutations impact development and differentiation, stem cell biology and cell fate in general, including various forms of cell death and cellular senescence. The study of genome instability in human molecular epidemiology and in relation to complex phenotypes, such as human disease, is considered a growing area of importance. Mechanisms of (epi)mutation induction, for example, during DNA repair, replication or recombination; novel methods of (epi)mutation detection, with a focus on ultra-high-throughput sequencing. Landscape of somatic mutations and epimutations in cancer and aging. Role of de novo mutations in human disease and aging; mutations in population genomics. Interactions between mutations and epimutations. The role of epimutations in chromatin structure and function. Mitochondrial DNA mutations and their consequences in terms of human disease and aging. Novel ways to generate mutations and epimutations in cell lines and animal models.