Genome-wide analysis to identify pathways affecting telomere-initiated senescence in budding yeast.
Genome-wide analysis to identify pathways affecting telomere-initiated senescence in budding yeast.
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DOI：
10.1534/g3.111.000216
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发表时间：
2011-08
期刊：
影响因子：
--
通讯作者：
Lydall D
中科院分区：
文献类型：
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作者：
Chang HY;Lawless C;Addinall SG;Oexle S;Taschuk M;Wipat A;Wilkinson DJ;Lydall D
在端粒酶缺失的酵母细胞中，就像哺乳动物细胞一样，端粒在许多世代中不断缩短，直到达到衰老/危机时期。在此之后，一小部分细胞可以逃脱衰老，主要是利用重组依赖的机制。为了研究影响进入端粒驱动的衰老和从端粒驱动的衰老恢复的途径，我们将基因缺失扰乱端粒酶(Est1Δ)与系统的酵母缺失收集相结合，并在高通量分析中测量了衰老特性。正如预期的那样，绝大多数基因缺失对进入/退出衰老没有强烈的影响。然而，大约200个基因缺失的行为类似于rad52Δest1Δ原型(rad52Δ影响同源重组)，加速进入衰老，这样的细胞通常不能恢复生长。数量较少的类似Rif1ΔEst1Δ原型(Rif1Δ影响结合端粒的蛋白质)的菌株加速进入衰老，但也加速从衰老中恢复。我们的全基因组分析确定了影响进入和/或退出端粒启动的衰老的基因，并将对研究端粒生物学、复制衰老、癌症和衰老的人感兴趣。我们的数据集是对其他与端粒生物学、遗传稳定性和DNA损伤反应相关的高通量研究的补充。
In telomerase-deficient yeast cells, like equivalent mammalian cells, telomeres shorten over many generations until a period of senescence/crisis is reached. After this, a small fraction of cells can escape senescence, principally using recombination-dependent mechanisms. To investigate the pathways that affect entry into and recovery from telomere-driven senescence, we combined a gene deletion disrupting telomerase (est1Δ) with the systematic yeast deletion collection and measured senescence characteristics in high-throughput assays. As expected, the vast majority of gene deletions showed no strong effects on entry into/exit from senescence. However, around 200 gene deletions behaving similarly to a rad52Δest1Δ archetype (rad52Δ affects homologous recombination) accelerated entry into senescence, and such cells often could not recover growth. A smaller number of strains similar to a rif1Δest1Δ archetype (rif1Δ affects proteins that bind telomeres) accelerated entry into senescence but also accelerated recovery from senescence. Our genome-wide analysis identifies genes that affect entry into and/or exit from telomere-initiated senescence and will be of interest to those studying telomere biology, replicative senescence, cancer, and ageing. Our dataset is complementary to other high-throughput studies relevant to telomere biology, genetic stability, and DNA damage responses.
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