2021
DOI: 10.1093/nar/gkab942
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CST does not evict elongating telomerase but prevents initiation by ssDNA binding

Abstract: The CST complex (CTC1-STN1-TEN1) has been shown to inhibit telomerase extension of the G-strand of telomeres and facilitate the switch to C-strand synthesis by DNA polymerase alpha-primase (pol α-primase). Recently the structure of human CST was solved by cryo-EM, allowing the design of mutant proteins defective in telomeric ssDNA binding and prompting the reexamination of CST inhibition of telomerase. The previous proposal that human CST inhibits telomerase by sequestration of the DNA primer was tested with a… Show more

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Cited by 27 publications
(37 citation statements)
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References 42 publications
(46 reference statements)
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“…Both of these protein complexes share functions 5,6 and structural homology 7 . At mammalian telomeres, CST inhibits extension of telomere G-rich overhangs 8,9 and facilitates pol-α/primase to synthesize the complementary C-strand. The latter process is known as the telomere C-strand fill-in 10,11 .…”
Section: Mainmentioning
confidence: 99%
“…Both of these protein complexes share functions 5,6 and structural homology 7 . At mammalian telomeres, CST inhibits extension of telomere G-rich overhangs 8,9 and facilitates pol-α/primase to synthesize the complementary C-strand. The latter process is known as the telomere C-strand fill-in 10,11 .…”
Section: Mainmentioning
confidence: 99%
“…When we express recombinant human CST in HEK-293T cells, the affinity-purified CST also contains the four subunits of Polα-primase 11 . Because Polα-primase is not overexpressed, it represents the naturally occurring enzyme.…”
Section: Cst Determines Origins Of C-strand Synthesismentioning
confidence: 99%
“…If telomeric repeats indeed define origins of priming and replication due to the DNA-binding specificity of CST, then C-strand synthesis should require the DNA-binding activity of CST. We tested this hypothesis with two DNA-binding mutants of the CTC1 subunit of CST, both of which still bind Polα-primase 11 . Each mutant has groups ('g') of two or three amino acids mutated.…”
Section: Cst Can Recruit Polα-primase To Non-telomeric Sequencesmentioning
confidence: 99%
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