Repair of DNA Damage Induced by the Cytidine Analog Zebularine Requires ATR and ATM in Arabidopsis

Plant Cell. 2015 Jun;27(6):1788-800. doi: 10.1105/tpc.114.135467. Epub 2015 May 28.

Abstract

DNA damage repair is an essential cellular mechanism that maintains genome stability. Here, we show that the nonmethylable cytidine analog zebularine induces a DNA damage response in Arabidopsis thaliana, independent of changes in DNA methylation. In contrast to genotoxic agents that induce damage in a cell cycle stage-independent manner, zebularine induces damage specifically during strand synthesis in DNA replication. The signaling of this damage is mediated by additive activity of ATAXIA TELANGIECTASIA MUTATED AND RAD3-RELATED and ATAXIA TELANGIECTASIA MUTATED kinases, which cause postreplicative cell cycle arrest and increased endoreplication. The repair requires a functional STRUCTURAL MAINTENANCE OF CHROMOSOMES5 (SMC5)-SMC6 complex and is accomplished predominantly by synthesis-dependent strand-annealing homologous recombination. Here, we provide insight into the response mechanism for coping with the genotoxic effects of zebularine and identify several components of the zebularine-induced DNA damage repair pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arabidopsis / genetics
  • Arabidopsis / physiology*
  • Arabidopsis Proteins / physiology
  • Ataxia Telangiectasia Mutated Proteins / physiology*
  • Cell Cycle / drug effects
  • Cytidine / analogs & derivatives*
  • Cytidine / pharmacology
  • DNA Damage / drug effects*
  • DNA Repair / physiology*
  • DNA Replication / drug effects

Substances

  • ATM protein, Arabidopsis
  • Arabidopsis Proteins
  • Cytidine
  • pyrimidin-2-one beta-ribofuranoside
  • ATR protein, Arabidopsis
  • Ataxia Telangiectasia Mutated Proteins