CST complex
The CST complex is a cellular multiprotein complex involved in telomere maintenance. In budding yeast (Saccharomyces cerevisiae), it is composed of the proteins Cdc13, Stn1, and Ten1; in mammals, it consists of the proteins CTC1, STN1, and TEN1.{{cite journal | vauthors = Price CM, Boltz KA, Chaiken MF, Stewart JA, Beilstein MA, Shippen DE | title = Evolution of CST function in telomere maintenance | journal = Cell Cycle | volume = 9 | issue = 16 | pages = 3157–65 | date = August 2010 | pmid = 20697207 | pmc = 3041159 | doi = 10.4161/cc.9.16.12547 }} It is related to the replication protein A complex.
Structure
{{Missing information|section|Resolved structures of yeast and human CST; different stoichiometry and human CST similarity to RPA|date=December 2020}}
For budding yeast as well as for mammals, CST is a protein heterotrimer, consisting of three distinct proteins. Yeast Stn1 and Ten1 are orthologous proteins to mammalian STN1 and TEN1.{{cite journal | vauthors = Sun J, Yu EY, Yang Y, Confer LA, Sun SH, Wan K, Lue NF, Lei M | title = Stn1-Ten1 is an Rpa2-Rpa3-like complex at telomeres | journal = Genes & Development | volume = 23 | issue = 24 | pages = 2900–14 | date = December 2009 | pmid = 20008938 | pmc = 2800091 | doi = 10.1101/gad.1851909 }} But yeast Cdc13 and mammalian CTC1 are very different in amino acid sequence, length, and to some extent in function.{{cite journal | vauthors = Rice C, Skordalakes E | title = Structure and function of the telomeric CST complex | journal = Computational and Structural Biotechnology Journal | volume = 14 | pages = 161–7 | year = 2016 | pmid = 27239262 | pmc = 4872678 | doi = 10.1016/j.csbj.2016.04.002 }}{{cite journal | vauthors = Yu EY, Sun J, Lei M, Lue NF | title = Analyses of Candida Cdc13 orthologues revealed a novel OB fold dimer arrangement, dimerization-assisted DNA binding, and substantial structural differences between Cdc13 and RPA70 | journal = Molecular and Cellular Biology | volume = 32 | issue = 1 | pages = 186–98 | date = January 2012 | pmid = 22025677 | pmc = 3255709 | doi = 10.1128/MCB.05875-11 }}
Function
For both budding yeast and mammals, the CST complex contributes to telomere maintenance, but this function is more crucial for budding yeast, where the CST complex performs the functions that shelterin performs in vertebrates. At least four factors contribute to telomere maintenance: telomerase, shelterin, TERRA and the CST Complex.{{cite journal | vauthors = Giraud-Panis MJ, Teixeira MT, Géli V, Gilson E | title = CST meets shelterin to keep telomeres in check | journal = Molecular Cell | volume = 39 | issue = 5 | pages = 665–76 | date = September 2010 | pmid = 20832719 | doi = 10.1016/j.molcel.2010.08.024 | doi-access = free }} CST protection of telomeres for mammals occurs under conditions of replication stress. But when not replicating DNA, mammals primarily require shelterin for telomere protection.{{cite journal | vauthors = Stewart JA, Wang F, Chaiken MF, Kasbek C, Chastain PD, Wright WE, Price CM | title = Human CST promotes telomere duplex replication and general replication restart after fork stalling | journal = The EMBO Journal | volume = 31 | issue = 17 | pages = 3537–49 | date = August 2012 | pmid = 22863775 | pmc = 3433780 | doi = 10.1038/emboj.2012.215 }} T-loops and G-quadruplexes are described as the two tertiary DNA structures that protect telomere ends and regulate telomere length. In fungus, the CST complex has been shown to unfold higher order G-tailed structures, such as occur with telomere exposure during DNA replication.{{cite journal | vauthors = Lue NF, Zhou R, Chico L, Mao N, Steinberg-Neifach O, Ha T | title = The telomere capping complex CST has an unusual stoichiometry, makes multipartite interaction with G-Tails, and unfolds higher-order G-tail structures | journal = PLOS Genetics | volume = 9 | issue = 1 | pages = e1003145 | year = 2013 | pmid = 23300477 | pmc = 3536697 | doi = 10.1371/journal.pgen.1003145 | doi-access = free }}