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有丝分裂延长:检测应激和受损细胞的关键指标。

Prolonged mitosis: A key indicator for detecting stressed and damaged cells.

作者信息

Sparr Carmen, Meitinger Franz

机构信息

Okinawa Institute of Science and Technology Graduate University, Okinawa 904-0495, Japan.

Okinawa Institute of Science and Technology Graduate University, Okinawa 904-0495, Japan.

出版信息

Curr Opin Cell Biol. 2025 Feb;92:102449. doi: 10.1016/j.ceb.2024.102449. Epub 2024 Dec 24.

Abstract

During mitosis, chromosomes condense, align to form a metaphase plate and segregate to the two daughter cells. Mitosis is one of the most complex recurring transformations in the life of a cell and requires a high degree of reliability to ensure the error-free transmission of genetic information to the next cell generation. An abnormally prolonged mitosis indicates potential defects that compromise genomic integrity. The mitotic stopwatch pathway detects even moderately prolonged mitoses by integrating memories of mitotic durations, ultimately leading to p53-mediated cell cycle arrest or death. This mechanism competes with mitogen signaling to stop the proliferation of damaged and potentially dangerous cells at a pre-oncogenic stage. Mitosis is a highly vulnerable phase, which is affected by multiple types of cellular damages and diverse stresses. We discuss the hypothesis that the duration of mitosis serves as an indicator of cell health.

摘要

在有丝分裂过程中,染色体浓缩,排列形成中期板,并分离到两个子细胞中。有丝分裂是细胞生命中最复杂的周期性转变之一,需要高度的可靠性来确保遗传信息无差错地传递给下一代细胞。异常延长的有丝分裂表明存在损害基因组完整性的潜在缺陷。有丝分裂计时途径通过整合有丝分裂持续时间的记忆来检测即使是适度延长的有丝分裂,最终导致p53介导的细胞周期停滞或死亡。这种机制与有丝分裂原信号传导竞争,以在致癌前阶段阻止受损和潜在危险细胞的增殖。有丝分裂是一个高度脆弱的阶段,受到多种类型的细胞损伤和各种应激的影响。我们讨论了有丝分裂持续时间作为细胞健康指标的假说。

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