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This review details molecular mechanisms, including the CIP2A–TOPBP1 complex, micronuclei formation, chromatin bridge processing, DNA damage repair, and mitotic checkpoints, and highlights therapeutic target opportunities.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & 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chromothripsis?",{"text":72,"@type":64},"The review emphasizes mechanisms including the CIP2A–TOPBP1 complex, micronuclei formation, chromatin bridge processing, DNA damage repair, and mitotic checkpoints.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},332625,1790838916,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,111,115,120,123,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & 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16(4), mjae016 [https://doi.org/10.1093/jmcb/mjae016](https://doi.org/10.1093/jmcb/mjae016)  \nPublished online May 6, 2024  \nReview  \nChromothripsis: an emerging crossroad from aberrant mitosis to therapeutic opportunities  \nUmer Ejaz1 , 2 , Zhen Dou 1 , 2 , Phil Y. Yao3 , Zhikai Wang1 , 2 , Xing Liu 1 , 2 , * , and Xuebiao Yao1 , *  \n1 MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, University of Science and Technology of China School of Life Sciences, Hefei 230027, China  \n2 Anhui Key Laboratory for Chemical Biology, Hefei National Science Center for Inter-disciplinary Sciences, Hefei 230027, China  \n3 University of California San Diego School of Medicine, San Diego, CA 92103, USA  \n* Correspondence to: Xing Liu, [E-mail:](E-mail: xing1017@ustc.edu.cn)[ xing1017@ustc.edu.cn](E-mail: xing1017@ustc.edu.cn); Xuebiao Yao, E-mail: [yaoxb@ustc.edu.cn](yaoxb@ustc.edu.cn)  \nEdited by Zhiyuan Shen  \nChromothripsis, 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.  \nKeywords: genomic stability, DNA damage repair, chromothripsis, synthetic lethality, cell division  \nIntroduction  \nCell division is the process by which one cell propagatesits genetic materials into two genetically identical daughter cells through segregation of chromosomes (Cleveland et al., 2003 ; Liu et al., 2020) . Chromosomes are thread-like structures comprised of proteins and DNA organized in a compact manner to allow the accurate and equal distribution of genetic materials to daughter cells during mitosis (Liu et al., 2020) . Although a century of study might leave the impression that most of the important mechanisms of chromosome segregation have already been discovered, many fundamental questions remain. For example, how do daughter cells decondense chromosomes to resemble the interphase chromosome territory and  \nReceived September 19, 2023 . Revised February 23, 2024 . Accepted May 4, 2024 .© The Author(s) (2024) . Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, CEMCS, CAS.  \nThis is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License ([https://creativecommons.org/licenses/by](https://creativecommons.org/licenses/by)nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use,  \nplease contact [journals.permissions@oup.com](journals.permissions@oup.com)  \ninter-chromosome interactions of the parent cell and what happens if a chromosome structure is ruptured during cell division (Figure 1A) .  \nOrche","cbCaie1DxoHiDaLa","https://ap.wps.com/l/cbCaie1DxoHiDaLa","pdf",1664384,16,"English","# Introduction\n# Chromothripsis and genomic instability\n## Mechanistic triggers during mitosis\n## Consequences: micronuclei, chromatin bridges, aneuploidy\n# Molecular entities and pathways\n## CIP2A–TOPBP1 complex\n## DNA damage repair and mitotic checkpoints\n# Therapeutic opportunities\n## Potential targets and underlying mechanisms","[{\"question\":\"What triggers chromothripsis according to the review?\",\"answer\":\"Chromothripsis is triggered by chromosome mis-segregation during mitosis, which leads to formation of aberrant structural entities such as micronuclei or chromatin bridges.\"},{\"question\":\"How does chromothripsis relate to cancer and disease prognosis?\",\"answer\":\"Chromothripsis is associated with cancer and can contribute to tumorigenesis, influencing how diseases develop and potentially affecting prognosis.\"},{\"question\":\"Which molecular processes does the review highlight as central to chromothripsis?\",\"answer\":\"The review emphasizes mechanisms including the CIP2A–TOPBP1 complex, micronuclei formation, chromatin bridge processing, DNA damage repair, and mitotic checkpoints.\"}]","Chromothripsis: an emerging crossroad from aberrant mitosis to therapeutic opportunities | PDF",1789998947]