Role of STN1 and DNA polymerase α in telomere stability and genome-wide replication in Arabidopsis

PLoS Genet. 2014 Oct 9;10(10):e1004682. doi: 10.1371/journal.pgen.1004682. eCollection 2014 Oct.

Abstract

The CST (Cdc13/CTC1-STN1-TEN1) complex was proposed to have evolved kingdom specific roles in telomere capping and replication. To shed light on its evolutionary conserved function, we examined the effect of STN1 dysfunction on telomere structure in plants. STN1 inactivation in Arabidopsis leads to a progressive loss of telomeric DNA and the onset of telomeric defects depends on the initial telomere size. While EXO1 aggravates defects associated with STN1 dysfunction, it does not contribute to the formation of long G-overhangs. Instead, these G-overhangs arise, at least partially, from telomerase-mediated telomere extension indicating a deficiency in C-strand fill-in synthesis. Analysis of hypomorphic DNA polymerase α mutants revealed that the impaired function of a general replication factor mimics the telomeric defects associated with CST dysfunction. Furthermore, we show that STN1-deficiency hinders re-replication of heterochromatic regions to a similar extent as polymerase α mutations. This comparative analysis of stn1 and pol α mutants suggests that STN1 plays a genome-wide role in DNA replication and that chromosome-end deprotection in stn1 mutants may represent a manifestation of aberrant replication through telomeres.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arabidopsis / genetics*
  • Arabidopsis / metabolism
  • Arabidopsis Proteins / genetics
  • Arabidopsis Proteins / metabolism*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • DNA Polymerase I / genetics
  • DNA Polymerase I / metabolism
  • DNA Replication
  • Exodeoxyribonucleases / metabolism
  • Genome, Plant
  • Heterochromatin / genetics
  • Heterochromatin / metabolism
  • Mutation
  • Telomerase / genetics
  • Telomerase / metabolism
  • Telomere* / metabolism

Substances

  • Arabidopsis Proteins
  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Heterochromatin
  • STN1 protein, Arabidopsis
  • XR5 protein, Arabidopsis
  • TERT protein, Arabidopsis
  • Telomerase
  • DNA Polymerase I
  • Exodeoxyribonucleases
  • exodeoxyribonuclease I

Grant support

This work was supported by the Austrian Science Fund (grant FWF #Y418-B03; http://www.fwf.ac.at) and by the Austrian Academy of Sciences (http://www.oeaw.ac.at/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.