The Consequences of Chromosome Segregation Errors in Mitosis and Meiosis.
The Consequences of Chromosome Segregation Errors in Mitosis and Meiosis.
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DOI：
10.3390/biology6010012
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发表时间：
2017-02-08
期刊：
影响因子：
4.2
通讯作者：
Gorbsky GJ
中科院分区：
文献类型：
--
作者：
Potapova T;Gorbsky GJ
细胞分裂过程中的错误常常导致染色体含量的改变，产生非整倍体或多倍体后代细胞。多倍体细胞随后可能发生异常分裂，产生非整倍体细胞。染色体分离错误也可能涉及整个染色体的片段。分离缺陷的一个主要后果是来自错误分离染色体上的基因的相对产物剂量的变化。转录调控因子的异常表达也可以影响正确分离的染色体上的基因。这些基因表达扰动的后果取决于受影响的特定染色体和非整倍体表型与环境的相互作用。大多数情况下，这些新的染色体分布对生物体的健康和生存是有害的。然而，在改变的环境中，基因拷贝数的改变可能产生更高度适应的表型。染色体分离错误对人类健康也有重要影响。它们可能促进病原微生物的耐药性。在癌细胞中，它们是遗传和表型变异的来源，可能会选择恶性肿瘤增加和治疗抵抗的人群。最后，减数分裂过程中配子形成过程中的染色体分离错误是人类出生缺陷和不孕症的主要原因。本文综述了有丝分裂和减数分裂错误的后果，重点介绍了新概念和人类健康。
Mistakes during cell division frequently generate changes in chromosome content, producing aneuploid or polyploid progeny cells. Polyploid cells may then undergo abnormal division to generate aneuploid cells. Chromosome segregation errors may also involve fragments of whole chromosomes. A major consequence of segregation defects is change in the relative dosage of products from genes located on the missegregated chromosomes. Abnormal expression of transcriptional regulators can also impact genes on the properly segregated chromosomes. The consequences of these perturbations in gene expression depend on the specific chromosomes affected and on the interplay of the aneuploid phenotype with the environment. Most often, these novel chromosome distributions are detrimental to the health and survival of the organism. However, in a changed environment, alterations in gene copy number may generate a more highly adapted phenotype. Chromosome segregation errors also have important implications in human health. They may promote drug resistance in pathogenic microorganisms. In cancer cells, they are a source for genetic and phenotypic variability that may select for populations with increased malignance and resistance to therapy. Lastly, chromosome segregation errors during gamete formation in meiosis are a primary cause of human birth defects and infertility. This review describes the consequences of mitotic and meiotic errors focusing on novel concepts and human health.