Hector Ronald E, Ray Alo, Chen Bo-Ruei, Shtofman Rebecca, Berkner Kathleen L, Runge Kurt W
Department of Molecular Genetics, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, Lerner Research Institute, 9500 Euclid Avenue, NE20, Cleveland, OH 44195, USA.
Chromosoma. 2012 Jun;121(3):277-90. doi: 10.1007/s00412-011-0359-0.
In many organisms, telomere DNA consists of simple sequence repeat tracts that are required to protect the chromosome end. In the yeast Saccharomyces cerevisiae, tract maintenance requires two checkpoint kinases of the ATM family, Tel1p and Mec1p. Previous work has shown that Tel1p is recruited to functional telomeres with shorter repeat tracts to promote telomerase-mediated repeat addition, but the role of Mec1p is unknown. We found that Mec1p telomere association was detected as cells senesced when telomere function was compromised by extreme shortening due to either the loss of telomerase or the double-strand break binding protein Ku. Exonuclease I effects the removal of the 5' telomeric strand, and eliminating it prevented both senescence and Mec1p telomere association. Thus, in contrast to Tel1p, Mec1p associates with short, functionally compromised telomeres.
在许多生物体中,端粒DNA由保护染色体末端所需的简单序列重复序列组成。在酿酒酵母中,序列维持需要ATM家族的两种检查点激酶Tel1p和Mec1p。先前的研究表明,Tel1p被招募到具有较短重复序列的功能性端粒上,以促进端粒酶介导的重复序列添加,但Mec1p的作用尚不清楚。我们发现,当端粒功能因端粒酶缺失或双链断裂结合蛋白Ku导致的极端缩短而受损时,随着细胞衰老可检测到Mec1p与端粒的结合。核酸外切酶I影响5'端粒链的去除,消除它可防止衰老和Mec1p与端粒的结合。因此,与Tel1p相反,Mec1p与短的、功能受损的端粒结合。