Cdc13 OB2 Dimerization Required for Productive Stn1 Binding and Efficient Telomere Maintenance
Cdc13 OB2 Dimerization Required for Productive Stn1 Binding and Efficient Telomere Maintenance
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DOI：
10.1016/j.str.2012.10.012
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发表时间：
2013-01-08
期刊：
影响因子：
5.7
通讯作者：
Skordalakes, Emmanuel
中科院分区：
文献类型：
--
作者：
Mason, Mark;Wanat, Jennifer J.;Skordalakes, Emmanuel
cdc 13是调节端粒长度和基因组稳定性所必需的酵母蛋白。它通过其端粒帽的特性和调节端粒酶进入端粒来做到这一点。位于募集和DNA结合结构域之间的酿酒酵母Cdc 13结构域的晶体结构揭示了具有从蛋白质核心延伸的异常长的环的寡糖结合折叠（OB 2）。这些环参与了两个Cdc 13 OB 2折叠之间的广泛相互作用，导致稳定的同源二聚化。有趣的是，功能受损的cdc 13 -1突变抑制OB 2二聚化。生化分析表明OB 2不参与端粒DNA或Stn 1结合。然而，全长Cdc 13中OB 2二聚体的破坏会影响Cdc 13-Stn 1的结合，导致端粒长度失调，温度敏感性增加和Stn 1结合缺陷。因此，我们建议，二聚化的OB 2结构域的Cdc 13所需的适当Cdc 13，Stn 1，Ten 1（CST）组装和生产端粒帽。
Cdc13 is an essential yeast protein required for telomere length regulation and genome stability. It does so via its telomere-capping properties and by regulating telomerase access to the telomeres. The crystal structure of the Saccharomyces cerevisiae Cdc13 domain located between the recruitment and DNA binding domains reveals an oligonucleotide-oligosaccharide binding fold (OB2) with unusually long loops extending from the core of the protein. These loops are involved in extensive interactions between two Cdc13 OB2 folds leading to stable homodimerization. Interestingly, the functionally impaired cdc13-1 mutation inhibits OB2 dimerization. Biochemical assays indicate OB2 is not involved in telomeric DNA or Stn1 binding. However, disruption of the OB2 dimer in full-length Cdc13 affects Cdc13-Stn1 association, leading to telomere length deregulation, increased temperature sensitivity, and Stn1 binding defects. We therefore propose that dimerization of the OB2 domain of Cdc13 is required for proper Cdc13, Stn1, Ten1 (CST) assembly and productive telomere capping.