Repair of DNA Damage Induced by the Cytidine Analog Zebularine Requires ATR and ATM in Arabidopsis. Issue 6 (28th May 2015)

• Record Type: Journal Article
• Authors: Liu, Chun-Hsin; Finke, Andreas; Díaz, Mariana; Rozhon, Wilfried; Poppenberger, Brigitte; Baubec, Tuncay; Pecinka, Ales
• Is Part Of: The Plant Cell. Volume 27:Issue 6(2015)
• Page Start: 1788
• Page End: 1800
• Publication Date: 2015-05-28
• DOI: 10.1105/tpc.114.135467
• Languages: English
• ISSNs: 1040-4651

Abstract

Abstract : The cytidine analog zebularine triggers DNA damage at replication forks, which is signaled by ATR and ATM and detoxified by synthesis-dependent strand-annealing homologous recombination. 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.