Gao Hua, Cervantes Rachel B, Mandell Edward K, Otero Joel H, Lundblad Victoria
The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
Nat Struct Mol Biol. 2007 Mar;14(3):208-14. doi: 10.1038/nsmb1205. Epub 2007 Feb 11.
Cdc13, Stn1 and Ten1 are essential yeast proteins that both protect chromosome termini from unregulated resection and regulate telomere length. Cdc13, which localizes to telomeres through high-affinity binding to telomeric single-stranded DNA, has been extensively characterized, whereas the contribution(s) of the Cdc13-associated Stn1 and Ten1 proteins to telomere function have remained unclear. We show here that Stn1 and Ten1 are DNA-binding proteins with specificity for telomeric DNA substrates. Furthermore, Stn1 and Ten1 show similarities to Rpa2 and Rpa3, subunits of the heterotrimeric replication protein A (RPA) complex, which is the major single-stranded DNA-binding activity in eukaryotic cells. We propose that Cdc13, Stn1 and Ten1 function as a telomere-specific RPA-like complex. Identification of an RPA-like complex that is targeted to a specific region of the genome suggests that multiple RPA-like complexes have evolved, each making individual contributions to genomic stability.
Cdc13、Stn1和Ten1是酵母中的必需蛋白,它们既能保护染色体末端免受无节制的切除,又能调节端粒长度。Cdc13通过与端粒单链DNA的高亲和力结合而定位于端粒,已得到广泛研究,而与Cdc13相关的Stn1和Ten1蛋白对端粒功能的作用仍不清楚。我们在此表明,Stn1和Ten1是对端粒DNA底物具有特异性的DNA结合蛋白。此外,Stn1和Ten1与异源三聚体复制蛋白A(RPA)复合物的亚基Rpa2和Rpa3相似,RPA复合物是真核细胞中主要的单链DNA结合活性物质。我们提出,Cdc13、Stn1和Ten1作为一种端粒特异性的类RPA复合物发挥作用。鉴定出一种靶向基因组特定区域的类RPA复合物表明,多种类RPA复合物已经进化,每种复合物都对基因组稳定性做出各自的贡献。
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