CTC1-STN1 terminates telomerase while STN1-TEN1 enables C-strand synthesis during telomere replication in colon cancer cells

Xuyang Feng, Shih-Jui Hsu, Anukana Bhattacharjee, Yongyao Wang, Jiajie Diao and Carolyn M. Price ()
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Xuyang Feng: University of Cincinnati
Shih-Jui Hsu: University of Cincinnati
Anukana Bhattacharjee: University of Cincinnati
Yongyao Wang: University of Cincinnati
Jiajie Diao: University of Cincinnati
Carolyn M. Price: University of Cincinnati

Nature Communications, 2018, vol. 9, issue 1, 1-12

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.

Date: 2018
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DOI: 10.1038/s41467-018-05154-z

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