The Saccharomyces CDC13 protein is a single-strand TG(1-3) telomeric DNA-binding protein in vitro that affects telomere behavior in vivo
The Saccharomyces CDC13 protein is a single-strand TG(1-3) telomeric DNA-binding protein in vitro that affects telomere behavior in vivo
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DOI：
10.1073/pnas.93.24.13760
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发表时间：
1996-11-26
影响因子：
11.1
通讯作者：
Zakian, VA
中科院分区：
文献类型：
--
作者：
Lin, JJ;Zakian, VA
酵母端粒由约300 bp的C（1-3）A/TG（1-3）DNA组成。缺乏必需基因CDC 13活性的细胞显示出由DNA损伤传感（RAD 9细胞周期检查点）介导的细胞周期停滞，可能是因为它们表现出端粒和端粒邻近DNA的链特异性丢失[Garvik，B.，卡森，M. &哈特韦尔，L.等人（1995）Mol. Cell. Biol.15，6128-6138]，在大肠杆菌中表达或在酵母中过表达的Cdc 13 p与单链TG（1-3）DNA特异性结合，Cdc 13 p在体外显示的结合特异性表明，在体内它可以与短链、组成性单链TG（1-3）尾被认为在细胞周期的大多数时间存在于端粒以及长单链TG（1-3）位于酵母端粒附近的基因在转录上受到抑制，这种现象称为端粒位置效应。过表达Cdc 13 p突变形式的细胞在高温下具有降低的端粒位置效应。这些数据表明Cdc 13 p通过直接结合端粒DNA发挥功能，从而限制了其降解和转录的可及性，并将其与检测受损DNA的因子屏蔽。
Saccharomyces telomeres consist of approximate to 300 bp of C(1-3)A/TG(1-3) DNA. Cells lacking the activity of the essential gene CDC13 display a cell cycle arrest mediated by the DNA damage sensing, RAD9 cell cycle checkpoint, presumably because they exhibit strand-specific loss of telomeric and telomere-adjacent DNA [Garvik, B., Carson, M. & Hartwell, L. (1995) Mol. Cell. Biol. 15, 6128-6138], Cdc13p expressed in Escherichia coli or overexpressed in yeast bound specifically to single-strand TG(1-3) DNA, The specificity of binding displayed by Cdc13p in vitro indicates that in vivo it could bind to both the short, constitutive single-strand TG(1-3) tails thought to be present at telomeres at most times in the cell cycle as well as to the long single-strand TG(1-3) tails that are intermediates in telomere replication, Genes located near yeast telomeres are transcriptionally repressed, a phenomenon known as telomere position effect, Cells overexpressing a mutant form of Cdc13p had reduced telomere position effect at high temperatures, These data suggest that Cdc13p functions by binding directly to telomeric DNA, thereby limiting its accessibility to degradation and transcription as well as masking it from factors that detect damaged DNA.