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- W2884814418 abstract "Abstract Telomerase elongates the telomeric G-strand to prevent telomere shortening through conventional DNA replication. However, synthesis of the complementary C-strand by DNA polymerase α is also required to maintain telomere length. Polymerase α cannot perform this role without the ssDNA binding complex CST (CTC1-STN1-TEN1). Here we describe the roles of individual CST subunits in telomerase regulation and G-overhang maturation in human colon cancer cells. We show that CTC1-STN1 limits telomerase action to prevent G-overhang overextension. CTC1 −/− cells exhibit telomeric DNA damage and growth arrest due to overhang elongation whereas TEN1 −/− cells do not. However, TEN1 is essential for C-strand synthesis and TEN1 −/− cells exhibit progressive telomere shortening. DNA binding analysis indicates that CTC1-STN1 retains affinity for ssDNA but TEN1 stabilizes binding. We propose CTC1-STN1 binding is sufficient to terminate telomerase action but altered DNA binding dynamics renders CTC1-STN1 unable to properly engage polymerase α on the overhang for C-strand synthesis." @default.
- W2884814418 created "2018-08-03" @default.
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- W2884814418 date "2018-07-19" @default.
- W2884814418 modified "2023-10-16" @default.
- W2884814418 title "CTC1-STN1 terminates telomerase while STN1-TEN1 enables C-strand synthesis during telomere replication in colon cancer cells" @default.
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- W2884814418 doi "https://doi.org/10.1038/s41467-018-05154-z" @default.
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