Human CST has independent functions during telomere duplex replication and C-strand fill-in

Cell Rep. 2012 Nov 29;2(5):1096-103. doi: 10.1016/j.celrep.2012.10.007. Epub 2012 Nov 8.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • DNA / metabolism
  • DNA Polymerase I / metabolism
  • DNA Replication
  • G2 Phase
  • HCT116 Cells
  • HeLa Cells
  • Humans
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • S Phase
  • Telomerase / metabolism
  • Telomere / metabolism*
  • Telomere-Binding Proteins / antagonists & inhibitors
  • Telomere-Binding Proteins / genetics
  • Telomere-Binding Proteins / metabolism*


  • RNA, Small Interfering
  • Stn1 protein, human
  • Telomere-Binding Proteins
  • DNA
  • Telomerase
  • DNA Polymerase I