Mec1p和Tel1p检查点激酶通过抑制端粒融合,使人类化酵母能够耐受慢性端粒功能障碍。

The Mec1p and Tel1p checkpoint kinases allow humanized yeast to tolerate chronic telomere dysfunctions by suppressing telomere fusions.

作者信息

di Domenico Enea Gino, Auriche Cristina, Viscardi Valeria, Longhese Maria Pia, Gilson Eric, Ascenzioni Fiorentina

机构信息

Dipartimento di Biologia Cellulare e dello Sviluppo, Università di Roma "La Sapienza", Roma, Italy.

出版信息

DNA Repair (Amst). 2009 Feb 1;8(2):209-18. doi: 10.1016/j.dnarep.2008.10.005. Epub 2008 Nov 28.

Abstract

In this work we report that budding yeasts carrying human-type telomeric repeats at their chromosome termini show a chronic activation of the Rad53-dependent DNA damage checkpoint pathway and a G2/M cell cycle delay. Furthermore, in the absence of either TEL1/ATM or MEC1/ATR genes, which encodes phosphatidylinositol 3-kinase-related kinases (PIKKs), we detected telomere fusions, whose appearance correlates with a reduced cell viability and a high rate of genome instability. Based on sequence analysis, telomere fusions occurred primarily between ultrashort telomeres. Microcolony formation assays argue against the possibility that fusion-containing cells are eliminated by PIKK-dependent signalling. These findings reveal that humanized telomeres in yeast cells are sensed as a chronically damaged DNA but do not greatly impair cell viability as long as the cells have a functional DNA damage checkpoint.

摘要

在这项工作中,我们报道了在其染色体末端携带人类型端粒重复序列的出芽酵母表现出Rad53依赖性DNA损伤检查点途径的慢性激活和G2/M细胞周期延迟。此外,在编码磷脂酰肌醇3-激酶相关激酶(PIKKs)的TEL1/ATM或MEC1/ATR基因缺失的情况下,我们检测到端粒融合,其出现与细胞活力降低和基因组不稳定性高相关。基于序列分析,端粒融合主要发生在超短端粒之间。微菌落形成试验排除了含融合细胞被PIKK依赖性信号传导消除的可能性。这些发现表明,酵母细胞中的人源化端粒被感知为慢性受损的DNA,但只要细胞具有功能性DNA损伤检查点,就不会对细胞活力造成太大损害。

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