Chromothripsis: an emerging crossroad from aberrant mitosis to therapeutic opportunities.

IF 5.3 2区生物学 Q2 CELL BIOLOGY

Journal of Molecular Cell Biology Pub Date : 2024-09-30 DOI:10.1093/jmcb/mjae016

Umer Ejaz, Zhen Dou, Phil Y Yao, Zhikai Wang, Xing Liu, Xuebiao Yao

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引用次数: 0

Abstract

Chromothripsis, a type of complex chromosomal rearrangement originally known as chromoanagenesis, has been a subject of extensive investigation due to its potential role in various diseases, particularly cancer. Chromothripsis involves the rapid acquisition of tens to hundreds of structural rearrangements within a short period, leading to complex alterations in one or a few chromosomes. This phenomenon is triggered by chromosome mis-segregation during mitosis. Errors in accurate chromosome segregation lead to formation of aberrant structural entities such as micronuclei or chromatin bridges. The association between chromothripsis and cancer has attracted significant interest, with potential implications for tumorigenesis and disease prognosis. This review aims to explore the intricate mechanisms and consequences of chromothripsis, with a specific focus on its association with mitotic perturbations. Herein, we discuss a comprehensive analysis of crucial molecular entities and pathways, exploring the intricate roles of the CIP2A-TOPBP1 complex, micronuclei formation, chromatin bridge processing, DNA damage repair, and mitotic checkpoints. Moreover, the review will highlight recent advancements in identifying potential therapeutic targets and the underlying molecular mechanisms associated with chromothripsis, paving the way for future therapeutic interventions in various diseases.

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染色体三分裂：从异常有丝分裂到治疗机会的新兴十字路口。

染色体三分裂（Chromothripsis）是一种复杂的染色体重排，最初被称为染色体基因突变（chromoanagenesis），由于其在各种疾病（尤其是癌症）中的潜在作用，一直是广泛研究的主题。染色体三分裂是指在短时间内迅速获得数十至数百个结构重排，导致一条或几条染色体发生复杂的改变。这种现象是由有丝分裂过程中染色体的错误分离引发的。染色体准确分离的错误会导致微核或染色质桥等异常结构实体的形成。染色质三分裂与癌症之间的关联引起了人们的极大兴趣，并对肿瘤发生和疾病预后产生了潜在影响。本综述旨在探讨染色质三分裂的复杂机制和后果，特别关注染色质三分裂与有丝分裂扰动的关联。在此，我们将讨论对关键分子实体和途径的全面分析，探讨 CIP2A-TOPBP1 复合物、微核形成、染色质桥处理、DNA 损伤修复和有丝分裂检查点的复杂作用。此外，该综述还将重点介绍在确定潜在治疗靶点和与染色质三分裂相关的潜在分子机制方面取得的最新进展，从而为未来对各种疾病的治疗干预铺平道路。

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

Journal of Molecular Cell Biology CELL BIOLOGY-

CiteScore

9.60

自引率

1.80%

发文量

1383

期刊介绍： The Journal of Molecular Cell Biology ( JMCB ) is a full open access, peer-reviewed online journal interested in inter-disciplinary studies at the cross-sections between molecular and cell biology as well as other disciplines of life sciences. The broad scope of JMCB reflects the merging of these life science disciplines such as stem cell research, signaling, genetics, epigenetics, genomics, development, immunology, cancer biology, molecular pathogenesis, neuroscience, and systems biology. The journal will publish primary research papers with findings of unusual significance and broad scientific interest. Review articles, letters and commentary on timely issues are also welcome. JMCB features an outstanding Editorial Board, which will serve as scientific advisors to the journal and provide strategic guidance for the development of the journal. By selecting only the best papers for publication, JMCB will provide a first rate publishing forum for scientists all over the world.