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检查染色体分离情况。

Double-checking chromosome segregation.

机构信息

Chromosome Instability & Dynamics Group, i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto , Porto, Portugal.

Instituto de Biologia Molecular e Celular, Universidade do Porto , Porto, Portugal.

出版信息

J Cell Biol. 2023 May 1;222(5). doi: 10.1083/jcb.202301106. Epub 2023 Apr 5.

Abstract

Enduring chromosome segregation errors represent potential threats to genomic stability due to eventual chromosome copy number alterations (aneuploidy) and formation of micronuclei-key intermediates of a rapid mutational process known as chromothripsis that is found in cancer and congenital disorders. The spindle assembly checkpoint (SAC) has been viewed as the sole surveillance mechanism that prevents chromosome segregation errors during mitosis and meiosis. However, different types of chromosome segregation errors stemming from incorrect kinetochore-microtubule attachments satisfy the SAC and are more frequent than previously anticipated. Remarkably, recent works have unveiled that most of these errors are corrected during anaphase and only rarely result in aneuploidy or formation of micronuclei. Here, we discuss recent progress in our understanding of the origin and fate of chromosome segregation errors that satisfy the SAC and shed light on the surveillance, correction, and clearance mechanisms that prevent their transmission, to preserve genomic stability.

摘要

持久的染色体分离错误由于最终的染色体拷贝数改变(非整倍体)和微核的形成而对基因组稳定性构成潜在威胁,微核是一种快速突变过程的关键中间体,称为染色质碎裂,存在于癌症和先天性疾病中。纺锤体组装检查点(SAC)一直被视为唯一的监测机制,可防止有丝分裂和减数分裂过程中的染色体分离错误。然而,源自不正确的动粒-微管连接的不同类型的染色体分离错误满足 SAC 的要求,并且比以前预期的更为频繁。值得注意的是,最近的研究揭示了这些错误中的大多数在后期被纠正,很少导致非整倍体或微核的形成。在这里,我们讨论了我们对满足 SAC 的染色体分离错误的起源和命运的最新理解的进展,并阐明了防止其传播以维持基因组稳定性的监测、纠正和清除机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfc7/10082326/1ad4b1832890/JCB_202301106_Fig1.jpg

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