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酵母菌株缺失 Tel1p 和 Mec1p 后出现的染色体重排和非整倍性反映了两种不同机制的缺陷。

Chromosome rearrangements and aneuploidy in yeast strains lacking both Tel1p and Mec1p reflect deficiencies in two different mechanisms.

机构信息

Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA.

出版信息

Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11465-70. doi: 10.1073/pnas.1006281107. Epub 2010 Jun 7.

Abstract

The human ATM and ATR proteins participate in the DNA damage and DNA replication checkpoint pathways and are critical to maintaining genome stability. The Saccharomyces cerevisiae homologs of ATM and ATR are Tel1p and Mec1p, respectively. Haploid tel1 mec1 strains have very short telomeres and very high rates of chromosomal aberrations. Here, we examine genetic stability in tel1 mec1 diploid cells. In the absence of induced DNA damage, these yeast strains had very high frequencies of aneuploidy (both trisomy and monosomy) in addition to elevated rates of chromosome rearrangements. Although we found the aneuploidy in the tel1 mec1 diploids mimicked that observed in bub1 diploids, the tel1 mec1 diploids had a functional spindle assembly checkpoint. Restoration of wild-type telomere lengths in the tel1 mec1 strain substantially reduced the rate of chromosome rearrangements but had no effect on the frequency of aneuploidy.

摘要

人类 ATM 和 ATR 蛋白参与 DNA 损伤和 DNA 复制检查点途径,对维持基因组稳定性至关重要。酿酒酵母中 ATM 和 ATR 的同源物分别是 Tel1p 和 Mec1p。单倍体 tel1 mec1 菌株的端粒非常短,染色体畸变率非常高。在这里,我们研究了 tel1 mec1 二倍体细胞的遗传稳定性。在没有诱导 DNA 损伤的情况下,除了染色体重排率升高外,这些酵母菌株还具有非常高的非整倍体(三体和单体)频率。尽管我们发现 tel1 mec1 二倍体中的非整倍体与 bub1 二倍体中观察到的相似,但 tel1 mec1 二倍体具有功能的纺锤体组装检查点。在 tel1 mec1 菌株中恢复野生型端粒长度可大大降低染色体重排率,但对非整倍体频率没有影响。

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