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类RPA蛋白介导酵母端粒功能。

RPA-like proteins mediate yeast telomere function.

作者信息

Gao Hua, Cervantes Rachel B, Mandell Edward K, Otero Joel H, Lundblad Victoria

机构信息

The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.

出版信息

Nat Struct Mol Biol. 2007 Mar;14(3):208-14. doi: 10.1038/nsmb1205. Epub 2007 Feb 11.


DOI:10.1038/nsmb1205
PMID:17293872
Abstract

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.

摘要

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。

相似文献

[1]
RPA-like proteins mediate yeast telomere function.

Nat Struct Mol Biol. 2007-3

[2]
Structure prediction-driven genetics in Saccharomyces cerevisiae identifies an interface between the t-RPA proteins Stn1 and Ten1.

Genetics. 2010-2-15

[3]
Ten1p promotes the telomeric DNA-binding activity of Cdc13p: implication for its function in telomere length regulation.

Cell Res. 2009-7

[4]
Chromosome end protection plasticity revealed by Stn1p and Ten1p bypass of Cdc13p.

Nat Cell Biol. 2006-7

[5]
Sequence-specific binding to telomeric DNA is not a conserved property of the Cdc13 DNA binding domain.

Biochemistry. 2011-6-29

[6]
Distinct roles for yeast Stn1 in telomere capping and telomerase inhibition.

EMBO J. 2008-9-3

[7]
TEN1 is essential for CDC13-mediated telomere capping.

Genetics. 2009-9-14

[8]
The telomere capping complex CST has an unusual stoichiometry, makes multipartite interaction with G-Tails, and unfolds higher-order G-tail structures.

PLoS Genet. 2013-1-3

[9]
Evolution of CST function in telomere maintenance.

Cell Cycle. 2010-8-26

[10]
Cdc13 OB2 dimerization required for productive Stn1 binding and efficient telomere maintenance.

Structure. 2012-11-21

引用本文的文献

[1]
The yeast CST and Polα/primase complexes act in concert to ensure proper telomere maintenance and protection.

Nucleic Acids Res. 2025-4-10

[2]
The canonical RPA complex interacts with Est3 to regulate yeast telomerase activity.

Proc Natl Acad Sci U S A. 2025-2-18

[3]
Dysfunction of Telomeric Cdc13-Stn1-Ten1 Simultaneously Activates DNA Damage and Spindle Checkpoints.

Cells. 2024-9-25

[4]
Telomere C-Strand Fill-In Machinery: New Insights into the Human CST-DNA Polymerase Alpha-Primase Structures and Functions.

Subcell Biochem. 2024

[5]
Cdc13 exhibits dynamic DNA strand exchange in the presence of telomeric DNA.

Nucleic Acids Res. 2024-6-24

[6]
CST-polymerase α-primase solves a second telomere end-replication problem.

Nature. 2024-3

[7]
Human Bocavirus 1 NP1 acts as an ssDNA-binding protein to help AAV2 DNA replication and cooperates with RPA to regulate AAV2 capsid expression.

J Virol. 2024-3-19

[8]
Control of telomere length in yeast by SUMOylated PCNA and the Elg1 PCNA unloader.

Elife. 2023-8-2

[9]
RPA-like single-stranded DNA-binding protein complexes including CST serve as specialized processivity factors for polymerases.

Curr Opin Struct Biol. 2023-8

[10]
TERRA and Telomere Maintenance in the Yeast .

Genes (Basel). 2023-2-28

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