Chromothripsis:an emerging crossroad from aberrant mitosis to therapeutic opportunities  

作　　者：Umer Ejaz Zhen Dou Phil YYao Zhikai Wang Xing Liu Xuebiao Yao 

机构地区：[1]MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics,University of Science and Technology of China School of Life Sciences,Hefei 230027,China [2]Anhui Key Laboratory for Chemical Biology,Hefei National Science Center for Inter-disciplinary Sciences,Hefei 230027,China [3]University of California San Diego School of Medicine,San Diego,CA 92103,USA

出　　处：《Journal of Molecular Cell Biology》2024年第4期1-16,共16页分子细胞生物学报（英文版）

基　　金：supported by the Ministry of Science and Technology of China and the National Natural Science Foundation of China(2022YFA1303100,32090040,92254302,2022YFA0806800,91854203,31621002,2017YFA0503600,21922706,92153302 to X.L.,2022YFA1302700 to Z.W.);the Ministry of Education(IRT_17R102,20113402130010,YD2070006001 to X.L.);the Fundamental Research Funds for the Central Universities(WK2070000194 to X.L.);the University of Science and Technology of China Start-up Fund(KY9990000167 to Z.W.).

摘　　要：Shen 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.

关 键 词：genomic stability DNA damage repair chromothripsis synthetic lethality cell division 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]