Ungar Lior, Yosef Nir, Sela Yael, Sharan Roded, Ruppin Eytan, Kupiec Martin
Department of Molecular Microbiology and Biotechnology, Tel-Aviv University, Tel-Aviv 69978, Israel.
Nucleic Acids Res. 2009 Jul;37(12):3840-9. doi: 10.1093/nar/gkp259. Epub 2009 Apr 22.
Telomeres are structures composed of repetitive DNA and proteins that protect the chromosomal ends in eukaryotic cells from fusion or degradation, thus contributing to genomic stability. Although telomere length varies between species, in all organisms studied telomere length appears to be controlled by a dynamic equilibrium between elongating mechanisms (mainly addition of repeats by the enzyme telomerase) and nucleases that shorten the telomeric sequences. Two previous studies have analyzed a collection of yeast deletion strains (deleted for nonessential genes) and found over 270 genes that affect telomere length (Telomere Length Maintenance or TLM genes). Here we complete the list of TLM by analyzing a collection of strains carrying hypomorphic alleles of most essential genes (DAmP collection). We identify 87 essential genes that affect telomere length in yeast. These genes interact with the nonessential TLM genes in a significant manner, and provide new insights on the mechanisms involved in telomere length maintenance. The newly identified genes span a variety of cellular processes, including protein degradation, pre-mRNA splicing and DNA replication.
端粒是由重复DNA和蛋白质组成的结构,可保护真核细胞中的染色体末端免于融合或降解,从而有助于基因组稳定性。尽管端粒长度在不同物种之间有所不同,但在所有研究的生物体中,端粒长度似乎受延长机制(主要是由端粒酶添加重复序列)和缩短端粒序列的核酸酶之间的动态平衡控制。之前的两项研究分析了一组酵母缺失菌株(缺失非必需基因),发现超过270个影响端粒长度的基因(端粒长度维持或TLM基因)。在这里,我们通过分析一组携带大多数必需基因的亚效等位基因的菌株(DAmP文库)完成了TLM基因列表。我们鉴定出87个影响酵母端粒长度的必需基因。这些基因与非必需的TLM基因有显著的相互作用,并为端粒长度维持所涉及的机制提供了新的见解。新鉴定的基因涵盖多种细胞过程,包括蛋白质降解、前体mRNA剪接和DNA复制。