Human CST Has Independent Functions during Telomere Duplex Replication and C-Strand Fill-In

Feng Wang, Jason A. Stewart, Christopher Kasbek, Yong Zhao, Woodring E. Wright, Carolyn M. Price

Research output: Contribution to journalArticle

80 Scopus citations

Abstract

Human CST (CTC1-STN1-TEN1) is an RPA-like complex that is needed for efficient replication through the telomere duplex and genome-wide replication restart after fork stalling. Here, we show that STN1/CST has a second function in telomere replication during G-overhang maturation. Analysis of overhang structure after STN1 depletion revealed normal kinetics for telomerase-mediated extension in S phase but a delay in subsequent overhang shortening. This delay resulted from a defect in C-strand fill-in. Short telomeres exhibited the fill-in defect but normal telomere duplex replication, indicating that STN1/CST functions independently in these processes. Our work also indicates that the requirement for STN1/CST in telomere duplex replication correlates with increasing telomere length and replication stress. Our results provide direct evidence that STN1/CST participates in C-strand fill-in. They also demonstrate that STN1/CST participates in two mechanistically separate steps during telomere replication and identify CST as a replication factor that solves diverse replication-associated problems.

Original languageEnglish (US)
Pages (from-to)1096-1103
Number of pages8
JournalCell Reports
Volume2
Issue number5
DOIs
StatePublished - Nov 29 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Wang, F., Stewart, J. A., Kasbek, C., Zhao, Y., Wright, W. E., & Price, C. M. (2012). Human CST Has Independent Functions during Telomere Duplex Replication and C-Strand Fill-In. Cell Reports, 2(5), 1096-1103. https://doi.org/10.1016/j.celrep.2012.10.007