Functional conservation and divergence of arabidopsis VENOSA4 and human SAMHD1 in DNA repair
The 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 probable <i>Arabidopsis thaliana</i> ortholog of SAMHD1, also functions in DSB repair by HR. The <i>ven4</i> loss-of-function mutants showed increased DNA ploidy and deregulated DNA repair genes, suggesting DNA damage accumulation. Hydroxyurea, which blocks DNA replication and generates DSBs, induced <i>VEN4</i> expression. The <i>ven4</i> mutants were hypersensitive to hydroxyurea, with decreased DSB repair by HR. Metabolomic analysis of the strong <i>ven4-0</i> mutant 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.
Authors
- Sara Fontcuberta-Cervera (ORCID: https://orcid.org/0000-0001-9410-6946)
- Vı́ctor Quesada (ORCID: https://orcid.org/0000-0002-0965-8680)
- Marı́a Rosa Ponce (ORCID: https://orcid.org/0000-0003-0770-4230)
- Kensuke Kawade (ORCID: https://orcid.org/0000-0003-1701-4567)
- Hirokazu Tsukaya (ORCID: https://orcid.org/0000-0002-4430-4538)
- José Luis Micol (ORCID: https://orcid.org/0000-0002-0396-1750)
- Akira Oikawa (ORCID: https://orcid.org/0000-0001-7507-4256)
- Raquel Sarmiento‐Mañús (ORCID: https://orcid.org/0000-0001-6929-8034)
Institutions
- Universitat de Miguel Hernández d'Elx (ES)
- Tokyo University of Science (JP)
- National Institutes of Natural Sciences (JP)
- Kyoto University (JP)
- RIKEN Center for Sustainable Resource Science (JP)
- Saitama University (JP)
- The University of Tokyo (JP)
Publication Details
- Journal
- Heliyon
- Published
- 2024-12-10
- DOI
- https://doi.org/10.1016/j.heliyon.2024.e41019
- Citations
- 2
- Primary Topic
- DNA Repair Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.47
Funders
- Generalitat Valenciana
- Ministerio de Ciencia e Innovación
- Agencia Estatal de Investigación
- Exploratory Research Center on Life and Living Systems, National Institutes of Natural Sciences