Consequences of gaining an extra chromosome.
Consequences of gaining an extra chromosome.
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DOI：
10.1007/s10577-023-09732-w
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发表时间：
2023-08-25
影响因子：
2.6
通讯作者：
Torres, Eduardo M.
中科院分区：
文献类型：
--
作者：
Torres, Eduardo M.
染色体分离错误导致非整倍体是人类流产的主要原因。除性染色体外，人类存活的非整倍体包括染色体21、18或13的三体，分别导致唐氏、爱德华兹或帕托综合征。患有18或13三体的人在出生后不久就会死亡，而患有唐氏综合症的人可以活到成年，但有智力残疾，而且容易患上多种疾病。在细胞水平上，单个染色体分离错误导致细胞失去一条染色体是致命的。相反，获得染色体的细胞可以存活。一些研究支持这样一种假设，即获得一条染色体的额外拷贝会导致基因特异性表型和与该染色体内编码的基因身份无关的表型。后者被称为非整倍体相关表型，是本综述的重点。在酵母和人类细胞中观察到的保守的非整倍体相关表型包括活力降低、基因表达增加、蛋白质合成和周转增加、核形态异常和代谢改变。值得注意的是，非整倍体细胞的异常核形态与鞘脂从头合成的代谢需求增加有关。这些发现揭示了非整倍体在唐氏综合症中可能的病理作用的重要见解。尽管对细胞生理有不利影响，但非整倍体是癌细胞的标志。了解非整倍体如何影响细胞生理学，可以揭示非整倍体癌细胞必须克服的选择压力，以支持无限增殖。
Mistakes in chromosome segregation leading to aneuploidy are the primary cause of miscarriages in humans. Excluding sex chromosomes, viable aneuploidies in humans include trisomies of chromosomes 21, 18, or 13, which cause Down, Edwards, or Patau syndromes, respectively. While individuals with trisomy 18 or 13 die soon after birth, people with Down syndrome live to adulthood but have intellectual disabilities and are prone to multiple diseases. At the cellular level, mistakes in the segregation of a single chromosome leading to a cell losing a chromosome are lethal. In contrast, the cell that gains a chromosome can survive. Several studies support the hypothesis that gaining an extra copy of a chromosome causes gene-specific phenotypes and phenotypes independent of the identity of the genes encoded within that chromosome. The latter, referred to as aneuploidy-associated phenotypes, are the focus of this review. Among the conserved aneuploidy-associated phenotypes observed in yeast and human cells are lower viability, increased gene expression, increased protein synthesis and turnover, abnormal nuclear morphology, and altered metabolism. Notably, abnormal nuclear morphology of aneuploid cells is associated with increased metabolic demand for de novo synthesis of sphingolipids. These findings reveal important insights into the possible pathological role of aneuploidy in Down syndrome. Despite the adverse effects on cell physiology, aneuploidy is a hallmark of cancer cells. Understanding how aneuploidy affects cell physiology can reveal insights into the selective pressure that aneuploid cancer cells must overcome to support unlimited proliferation.
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影响因子：
16.6
作者：
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影响因子：
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作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1126/science.aaf8399
发表时间：
2017-01-20
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
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通讯作者：
Elledge SJ