Deficiency of the Arabidopsis helicase RTEL1 triggers a SOG1-dependent replication checkpoint in response to DNA cross-links

Plant Cell. 2015 Jan;27(1):149-61. doi: 10.1105/tpc.114.134312. Epub 2015 Jan 16.

Abstract

To maintain genome integrity, DNA replication is executed and regulated by a complex molecular network of numerous proteins, including helicases and cell cycle checkpoint regulators. Through a systematic screening for putative replication mutants, we identified an Arabidopsis thaliana homolog of human Regulator of Telomere Length 1 (RTEL1), which functions in DNA replication, DNA repair, and recombination. RTEL1 deficiency retards plant growth, a phenotype including a prolonged S-phase duration and decreased cell proliferation. Genetic analysis revealed that rtel1 mutant plants show activated cell cycle checkpoints, specific sensitivity to DNA cross-linking agents, and increased homologous recombination, but a lack of progressive shortening of telomeres, indicating that RTEL1 functions have only been partially conserved between mammals and plants. Surprisingly, RTEL1 deficiency induces tolerance to the deoxynucleotide-depleting drug hydroxyurea, which could be mimicked by DNA cross-linking agents. This resistance does not rely on the essential replication checkpoint regulator WEE1 but could be blocked by a mutation in the SOG1 transcription factor. Taken together, our data indicate that RTEL1 is required for DNA replication and that its deficiency activates a SOG1-dependent replication checkpoint.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arabidopsis / enzymology*
  • Arabidopsis / genetics
  • Arabidopsis / metabolism
  • Arabidopsis Proteins / genetics
  • Arabidopsis Proteins / metabolism*
  • DNA Damage / genetics
  • DNA Damage / physiology
  • DNA Helicases / deficiency
  • DNA Helicases / genetics
  • DNA Helicases / metabolism*
  • DNA Replication / genetics
  • DNA Replication / physiology
  • Plant Proteins / genetics
  • Plant Proteins / metabolism
  • Telomere / genetics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Arabidopsis Proteins
  • Plant Proteins
  • SOG1 protein, Arabidopsis
  • Transcription Factors
  • DNA Helicases
  • RTEL1 protein, Arabidopsis