From pathology to therapy: A comprehensive review of ATRX mutation related molecular functions and disorders

IF 6.4 2区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation Research-Reviews in Mutation Research Pub Date : 2025-01-01 DOI:10.1016/j.mrrev.2025.108537

Fan Xu , Daohan Yu , Jiazheng Guo , Jingze Hu , Yunlei Zhao , Chuanlu Jiang , Xiangqi Meng , Jinquan Cai , Yan Zhao

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引用次数: 0

Abstract

ATRX (alpha-thalassemia/mental retardation, X-linked), a chromatin remodeler, is one of the most commonly mutated genes in human cancer. The ATRX protein functions as a histone chaperone, facilitating the proper folding and assembly of histone proteins into nucleosome cores. Investigations into its molecular mechanisms have significantly advanced our understanding of its roles in diseases associated with chromosomal instability and defective DNA repair. In this comprehensive review, we delineate ATRX's critical function in maintaining heterochromatin integrity and genomic stability under physiological conditions. We further explore the pathogenesis of ATRX-deficient tumors and ATRX syndrome, systematically evaluate current therapeutic strategies for these conditions, and propose novel perspectives on potential targeted therapies for ATRX-mutated malignancies. This review provides useful resource for regarding the etiology and treatment of ATRX deficiency-related diseases.

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从病理到治疗：ATRX突变相关分子功能和疾病的综合综述

ATRX （α -地中海贫血/智力低下，x连锁）是一种染色质重塑基因，是人类癌症中最常见的突变基因之一。ATRX蛋白作为组蛋白伴侣蛋白，促进组蛋白正确折叠和组装成核小体核心。对其分子机制的研究大大提高了我们对其在染色体不稳定性和DNA修复缺陷相关疾病中的作用的理解。在这篇全面的综述中，我们描述了ATRX在生理条件下维持异染色质完整性和基因组稳定性的关键功能。我们进一步探讨了ATRX缺陷肿瘤和ATRX综合征的发病机制，系统评估了目前针对这些疾病的治疗策略，并提出了针对ATRX突变恶性肿瘤的潜在靶向治疗的新观点。本文综述为ATRX缺乏相关疾病的病因和治疗提供了有益的资源。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Mutation Research-Reviews in Mutation Research 生物-毒理学

CiteScore

12.20

自引率

1.90%

发文量

审稿时长

15.7 weeks

期刊介绍： The subject areas of Reviews in Mutation Research encompass the entire spectrum of the science of mutation research and its applications, with particular emphasis on the relationship between mutation and disease. Thus this section will cover advances in human genome research (including evolving technologies for mutation detection and functional genomics) with applications in clinical genetics, gene therapy and health risk assessment for environmental agents of concern.