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PreprintCited by 3DNA Repair MechanismsPlant Molecular Biology ResearchCRISPR and Genetic Engineering

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

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Sarmiento-Mañús, Raquel, Fontcuberta-Cervera, Sara, Kawade, Kensuke, Oikawa, Akira, Tsukaya, Hirokazu, Quesada, Víctor, Micol, José Luis, Ponce, María Rosa·2024·Heliyon
DOI 10.1101/2024.05.27.596045PMC PMC11720913

Preprint — published as 10.1016/j.heliyon.2024.e41019

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Abstract

SUMMARY: 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 Arabidopsis thaliana ortholog of SAMHD1, also functions in DSB repair by HR. The ven4 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 VEN4 expression. The ven4 mutants were hypersensitive to hydroxyurea, with decreased DSB repair by HR. Metabolomic analysis of the strong ven4-0 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. One sentence summary: Human SAMHD1 is involved in dNTP metabolism and DNA repair; the latter function is conserved in VEN4, its likely Arabidopsis ortholog.

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Metadata

Authors
Sarmiento-Mañús, R., Fontcuberta-Cervera, S., Kawade, K., Oikawa, A., Tsukaya, H., Quesada, V., Micol, J. L., & Ponce, M. R.
Affiliations
  • Universitat de Miguel Hernández d'Elx (ES)
  • RIKEN Center for Sustainable Resource Science (JP)
  • Kyoto University (JP)
  • The Exploratory Research Center on Life and Living Systems (JP)
Corresponding author
Micol, José Luis
ORCID
Venue
Heliyon
Publisher
openRxiv
Published
2024-05-31
Volume
11
Issue
1
Pages
e41019-e41019
ISSN
2405-8440 (ISSN-L)
DOI
10.1101/2024.05.27.596045
PMC
PMC11720913
OpenAlex
W4405234641
Cited by
3
References
1
Citations by year
2025: 3
FWCI
0.41
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Heliyon (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Generalitat Valenciana (CIPROM/2022/2)
  • Ministerio de Ciencia e Innovación (PGC2018-093445-B-I00, B-I00, PGC2018, PID2021-127725NB-I00, PID2020-117125RB-I00, PID2020)
  • Japan Society for the Promotion of Science (24H00566)
  • Agencia Estatal de Investigación (PGC2018-093445-B-I00)
  • Exploratory Research Center on Life and Living Systems, National Institutes of Natural Sciences
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
Keywords
SAMHD1, DNA double-strand break repair, homologous recombination, dNTPase, Arabidopsis thaliana, hydroxyurea sensitivity, DNA ploidy, DNA damage response, R-loops, functional conservation, functional divergence, metabolomics

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