Functional conservation and divergence of Arabidopsis VENOSA4 and human SAMHD1 in DNA repair

Abstract

SUMMARYThe human deoxyribonucleoside triphosphatase (dNTPase) Sterile alpha motif and histidine-aspartate domain containing protein 1 (SAMHD1) has a dNTPase-independent role in repairing DNA double-strand breaks (DSBs) by homologous recombination (HR). Here, we show that VENOSA4 (VEN4), the probableArabidopsis thalianaortholog of SAMHD1, also functions in DSB repair by HR. Theven4loss-of-function mutants showed increased DNA ploidy and deregulated DNA repair genes, suggesting DNA damage accumulation. Hydroxyurea, which blocks DNA replication and generates DSBs, inducedVEN4expression. Theven4mutants were hypersensitive to hydroxyurea, with decreased DSB repair by HR. Metabolomic analysis of the strongven4-0mutant revealed depletion of metabolites associated with DNA damage responses. In contrast to SAMHD1, VEN4 showed no evident involvement in preventing R-loop accumulation. Our study thus reveals functional conservation in DNA repair by VEN4 and SAMHD1.One sentence summaryHuman SAMHD1 is involved in dNTP metabolism and DNA repair; the latter function is conserved in VEN4, its likely Arabidopsis ortholog.