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

75 Citations (Scopus)

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

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Telomere
Defects
Telomerase
Genes
Kinetics
S Phase
Genome

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Human CST Has Independent Functions during Telomere Duplex Replication and C-Strand Fill-In. / Wang, Feng; Stewart, Jason A.; Kasbek, Christopher; Zhao, Yong; Wright, Woodring E.; Price, Carolyn M.

In: Cell Reports, Vol. 2, No. 5, 29.11.2012, p. 1096-1103.

Research output: Contribution to journalArticle

Wang, Feng ; Stewart, Jason A. ; Kasbek, Christopher ; Zhao, Yong ; Wright, Woodring E. ; Price, Carolyn M. / Human CST Has Independent Functions during Telomere Duplex Replication and C-Strand Fill-In. In: Cell Reports. 2012 ; Vol. 2, No. 5. pp. 1096-1103.
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