Synaptic vesicle glycoprotein 2 enables viable aneuploidy following centrosome amplification.

IF 5.1 3区生物学 Q2 GENETICS & HEREDITY

Genetics Pub Date : 2025-10-08 DOI:10.1093/genetics/iyaf148

Jane E Blackmer, Erin A Jezuit, Archan Chakraborty, Satya N Yalamanchi, Ruth A Montague, Erin E Dickert, Nora G Peterson, William Outlaw, Donald T Fox

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引用次数: 0

Abstract

Amplified centrosome number causes genomic instability, most severely through division into >2 aneuploid daughter cells (multipolar mitosis). Several mechanisms that suppress multipolar division have been uncovered, yet mechanisms that favor viable multipolar division are poorly understood. To uncover factors that promote viability in cells with frequent centrosome amplification and multipolar division, we conducted an unbiased Drosophila genetic screen. In 642 mutagenized lines, we exploited the ability of intestinal papillar cells to form and function despite multipolar divisions. Our top hit is an unnamed gene, CG3168. We name this gene synaptic vesicle glycoprotein 2, reflecting homology to human Synaptic Vesicle Glycoprotein 2 (SV2) proteins. GFP-tagged SV2 localizes to the plasma membrane. In cells with amplified centrosomes, SV2 positions membrane-adjacent centrosomes, which prevents severe errors in chromosome alignment and segregation. Our results uncover membrane-based multipolar division regulation and reveal a novel vulnerability in cells with common cancer properties.

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突触囊泡糖蛋白2使中心体扩增后的非整倍体存活。

中心体数量的扩增导致基因组不稳定，最严重的是分裂成两个以上的非整倍体子细胞（多极有丝分裂）。抑制多极分裂的几个机制已经被发现，但有利于可行的多极分裂的机制却知之甚少。为了揭示促进具有频繁中心体扩增和多极分裂的细胞活力的因素，我们进行了无偏倚的果蝇遗传筛选。在642个诱变系中，我们利用了肠乳头细胞在多极分裂的情况下形成和功能的能力。我们的头号目标是一个未命名的基因，CG3168。我们将该基因命名为突触囊泡糖蛋白2，反映了与人类突触囊泡糖蛋白2 （SV2）蛋白的同源性。gfp标记的SV2定位于质膜。在中心体扩增的细胞中，SV2定位于膜邻近的中心体，从而防止染色体排列和分离的严重错误。我们的研究结果揭示了基于膜的多极分裂调节，并揭示了具有常见癌症特性的细胞中的一种新的脆弱性。

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

Genetics GENETICS & HEREDITY-

CiteScore

6.90

自引率

6.10%

发文量

177

审稿时长

1.5 months

期刊介绍： GENETICS is published by the Genetics Society of America, a scholarly society that seeks to deepen our understanding of the living world by advancing our understanding of genetics. Since 1916, GENETICS has published high-quality, original research presenting novel findings bearing on genetics and genomics. The journal publishes empirical studies of organisms ranging from microbes to humans, as well as theoretical work. While it has an illustrious history, GENETICS has changed along with the communities it serves: it is not your mentor''s journal. The editors make decisions quickly – in around 30 days – without sacrificing the excellence and scholarship for which the journal has long been known. GENETICS is a peer reviewed, peer-edited journal, with an international reach and increasing visibility and impact. All editorial decisions are made through collaboration of at least two editors who are practicing scientists. GENETICS is constantly innovating: expanded types of content include Reviews, Commentary (current issues of interest to geneticists), Perspectives (historical), Primers (to introduce primary literature into the classroom), Toolbox Reviews, plus YeastBook, FlyBook, and WormBook (coming spring 2016). For particularly time-sensitive results, we publish Communications. As part of our mission to serve our communities, we''ve published thematic collections, including Genomic Selection, Multiparental Populations, Mouse Collaborative Cross, and the Genetics of Sex.