G2/M-checkpoint activation in fasciata1 rescues an aberrant S-phase checkpoint but causes genome instability

• DOI: 10.1093/plphys/kiab201
• Publication Date: 2021-05-04T20:43:03Z
• Authors: Thomas Eekhout; Martina Dvorackova; José Antonio Pedr...; Martina Nespor Da...; Pooneh Kalhorzadeh; Hilde Van den Daele; Ilse Vercauteren; Jiri Fajkus; Lieven De Veylder
• Keywords: DEPENDENT KINASE INHIBITORS; DNA Replication; Physiology; ASSEMBLY FACTOR-I; Arabidopsis; DNA-DAMAGE RESPONSE; Plant Science; Ataxia Telangiectasia Mutated Proteins; Protein Serine-Threonine Kinases; HOMOLOGOUS RECOMBINATION; Genomic Instability; Proto-Oncogene Proteins c-myb; 03 medical and health sciences; Stress, Physiological; Genetics; CAF-1; 0303 health sciences; Arabidopsis Proteins; Biology and Life Sciences; ATR; DIFFERENTIATION; REPLICATION; ARABIDOPSIS-THALIANA; 45S RDNA; Genome, Plant; Signal Transduction; Transcription Factors

Abstract The WEE1 and ATM AND RAD3-RELATED (ATR) kinases are important regulators of the plant intra-S-phase checkpoint; consequently, WEE1KO and ATRKO roots are hypersensitive to replication-inhibitory drugs. Here, we report on a loss-of-function mutant allele of the FASCIATA1 (FAS1) subunit of the chromatin assembly factor 1 (CAF-1) complex that suppresses the phenotype of WEE1- or ATR-deficient Arabidopsis (Arabidopsis thaliana) plants. We demonstrate that lack of FAS1 activity results in the activation of an ATAXIA TELANGIECTASIA MUTATED (ATM)- and SUPPRESSOR OF GAMMA-RESPONSE 1 (SOG1)-mediated G2/M-arrest that renders the ATR and WEE1 checkpoint regulators redundant. This ATM activation accounts for the telomere erosion and loss of ribosomal DNA that are described for fas1 plants. Knocking out SOG1 in the fas1 wee1 background restores replication stress sensitivity, demonstrating that SOG1 is an important secondary checkpoint regulator in plants that fail to activate the intra-S-phase checkpoint.