Evolution of CST function in telomere maintenance

Price, Carolyn M.; Boltz, Kara A.; Chaiken, Mary F.; Stewart, Jason A.; Beilstein, Mark A.; Shippen, Dorothy E.

doi:10.4161/cc.9.16.12547

Cited by 147 publications

(166 citation statements)

References 57 publications

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“…2). However, although we suspect that this clustering is of func tional significance, it is difficult to model the domain structure of CTC1 because of the high degree of sequence divergence from other proteins 12 . Of note, none of the 14 distinct, putatively pathogenic CTC1 variants have been annotated as polymorphisms in dbSNP.…”

mentioning

confidence: 97%

Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus

Anderson¹,

Kasher²,

Mayer³

et al. 2012

Nat Genet

247

237

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Coats plus is a highly pleiotropic disorder particularly affecting the eye, brain, bone and gastrointestinal tract. Here, we show that Coats plus results from mutations in CTC1, encoding conserved telomere maintenance component 1, a member of the mammalian homolog of the yeast heterotrimeric CST telomeric capping complex. Consistent with the observation of shortened telomeres in an Arabidopsis CTC1 mutant and the phenotypic overlap of Coats plus with the telomeric maintenance disorders comprising dyskeratosis congenita, we observed shortened telomeres in three individuals with Coats plus and an increase in spontaneous γH2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the α-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-α primase, the only enzyme known to initiate DNA replication in eukaryotic cells. Thus, CTC1 may have a function in DNA metabolism that is necessary for but not specific to telomeric integrity

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mentioning

confidence: 97%

Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus

Anderson¹,

Kasher²,

Mayer³

et al. 2012

Nat Genet

247

237

View full text Add to dashboard Cite

show abstract

“…Possibly more relevant for this is the CST complex, which binds to the telomerase-extended telomeric 3 0 end (Chen et al 2012). Indeed, human Ctc1 and Stn1 stimulate DNA polymerase a-primase, increasing its affinity for template DNA (Casteel et al 2009), and CST has been implicated in assisting lagging-strand synthesis at telomeres and other special DNA sequences throughout the genome (Miyake et al 2009;Price et al 2010;Gu et al 2012). How the binding of single-stranded telomeric DNA by telomere-binding proteins, which include Pot1-Tpp1, CST, RPA, and possibly hnRNPA1, is regulated is unclear, nor is it known how T-loop formation may be influenced by these factors, possibly in a cellcycle-dependent manner.…”

Section: Mammalsmentioning

confidence: 99%

Replication of Telomeres and the Regulation of Telomerase

Pfeiffer

Lingner

2013

Cold Spring Harbor Perspectives in Biology

112

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Telomeres are the physical ends of eukaryotic chromosomes. They protect chromosome ends from DNA degradation, recombination, and DNA end fusions, and they are important for nuclear architecture. Telomeres provide a mechanism for their replication by semiconservative DNA replication and length maintenance by telomerase. Through telomerase repression and induced telomere shortening, telomeres provide the means to regulate cellular life span. In this review, we introduce the current knowledge on telomere composition and structure. We then discuss in depth the current understanding of how telomere components mediate their function during semiconservative DNA replication and how telomerase is regulated at the end of the chromosome. We focus our discussion on the telomeres from mammals and the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe.

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“…Specific protein complexes, termed the shelterin and CST complexes, help to maintain the t-loop structure and regulate telomere access during DNA replication (e.g. for review, see [3]). Processes occur within cells not only to maintain telomere structure, but also to restore the loss of telomeric DNA that occurs as a natural consequence of the DNA replication process.…”

Section: Introductionmentioning

confidence: 99%