ArticleCell reports2017
SAMHD1 Promotes DNA End Resection to Facilitate DNA Repair by Homologous Recombination.
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Article in Cell reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers.
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133citing papers in PubMed
7.9field-weighted citation impact, top 2% of its field
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Who cites it
133 citing papers in PubMed, 208 citations in OpenAlex.
- p21 (CDKN1A) Is the Major Driver of Sulforaphane-Mediated Reduction in SAMHD1 T592 Phosphorylation in Macrophages.Biomolecules · 2026Article
- Nucleotide Metabolism in Health and Disease.MedComm · 2026Review
- cGAS-STING pathway in lung cancer and emerging therapeutic approaches.Drug discovery today · 2026Review
- Serum uric acid and its metabolism-a vital factor in the inflammatory transformation of cancer.Journal of advanced research · 2026Review
- Bloom syndrome helicase is required for efficient HIV-1 reverse transcription in macrophages.bioRxiv : the preprint server for biology · 2026Article
- Allosteric targeting with antiviral nucleotide analogs allows fine-tuning of SAMHD1 dNTPase activity.The Journal of biological chemistry · 2026Article
- Insight into the Biology of Hepatitis B Virus and Recent Therapeutic Approaches.Current microbiology · 2026Review
- Manipulation of the nucleotide pool in human, bacterial and plant immunity.Nature reviews. Immunology · 2026Review
- Hepatocyte SAMHD1 Deficiency Attenuates Hepatic Steatosis via Suppression of SREBP Activation in a Mouse Model of Metabolic-Associated Steatotic Liver Disease.International journal of biological sciences · 2026Article
- Large-scale drug sensitivity, gene dependency, and proteogenomic analyses of telomere maintenance mechanisms in cancer cells.Nature communications · 2025Article
- Selective depletion of tumor-associated SAMHD1 enhances chemotherapeutic efficacy and antitumor immune responses.Signal transduction and targeted therapy · 2025Article
- Impact of SAMHD1 and phosphorylated ATM levels on the progression and prognosis of patients with soft tissue sarcoma.Oncology letters · 2025Article
- Genome instability and crosstalk with the immune response.Genome medicine · 2025Review
- ssDNA and ssRNA Promote Phase Condensation of SAMHD1.Biochemistry · 2025Article
- Blockade ofmBio · 2025Article
- Mechanisms and regulation of DNA end resection in the maintenance of genome stability.Nature reviews. Molecular cell biology · 2025Review
- Genome-wide CRISPR activation screen identifies ARL11 as a sensitivity determinant of PARP inhibitor therapy.Cancer gene therapy · 2025Article
- Transcriptomic Analysis Reveals Key Pathways Influenced by HIV-2 Vpx.International journal of molecular sciences · 2025Article
- SAMHD1 dysfunction impairs DNA damage response and increases sensitivity to PARP inhibition in chronic lymphocytic leukemia.Scientific reports · 2025Article
- Transition State Analysis of SAMHD1 from PrimaryJournal of the American Chemical Society · 2025Article
73 more citing papers are in PubMed but not listed here.
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Authors and funding
28 authors at 4 institutions in 2 countries.
Waaqo DaddachaDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA; Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA.
Allyson E KoyenDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA; Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA.
Amanda J BastienDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA; Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA.
PamelaSara E HeadDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA; Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA.
Vishal R DhereDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA; Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA.
Geraldine N NabetaDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA; Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA.
Erin C ConnollyDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA; Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA.
Erica WernerDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA; Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA; Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA.
Matthew Z MaddenDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA; Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA.
Michele B DalyDepartment of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Elizabeth V MintenDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA; Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA.
Donna R WhelanDepartment of Biochemistry and Molecular Pharmacology, NYU School of Medicine, New York, NY 10016, USA.
Ashley J SchlafsteinDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA; Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA.
Hui ZhangDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA; Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA.
Roopesh AnandInstitute for Research in Biomedicine, Università della Svizzera italiana, Via Vela 6, 6500 Bellinzona, Switzerland.
Christine DoronioDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA; Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA.
Allison E WithersDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA; Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA.
Caitlin ShepardDepartment of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Ranjini K SundaramDepartment of Radiation Oncology, Yale University School of Medicine, New Haven, CT 06520, USA.
Xingming DengDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA; Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA.
William S DynanDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA; Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA; Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA.
Ya WangDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA; Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA.
Ranjit S BindraDepartment of Radiation Oncology, Yale University School of Medicine, New Haven, CT 06520, USA.
Petr CejkaInstitute for Research in Biomedicine, Università della Svizzera italiana, Via Vela 6, 6500 Bellinzona, Switzerland.
Eli RothenbergDepartment of Biochemistry and Molecular Pharmacology, NYU School of Medicine, New York, NY 10016, USA.
Paul W DoetschDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA; Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA; Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA.
Baek KimDepartment of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
David S YuDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA; Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA. Electronic address: dsyu@emory.edu.
Emory University · USNew York University · USUniversità della Svizzera italiana · CHYale University · US
Funding
Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9MMechanisms of transcriptional and replicative mutagenesisZIAES103328 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI DOETSCH, PAUL · 2018 to 2025
$10.5MReplication fidelity and lentiviral pathogenesisR01AI049781 · NIAID · UNIVERSITY OF ROCHESTER · PI KIM, BAEK · 2002 to 2016
$4.9MMechanisms of SIRT2 Function in the Replication Stress ResponseR01CA178999 · NCI · EMORY UNIVERSITY · PI YU, DAVID SUNG-WEN · 2013 to 2023
$3.5MStructure-based anti-cancer drug developmentR01CA136534 · NCI · EMORY UNIVERSITY · PI DENG, XINGMING · 2010 to 2020
$3.4MSee, Reach, Treat Tumor-Optimized Transarterial Chemoembolization DrugDeliveryR01CA160771 · NCI · YALE UNIVERSITY · PI GESCHWIND, JEAN-FRANCOIS H, LIN, MINGDE · 2011 to 2015
$2.6MSAMHD1 controls dNTP pool and HIV sensitivity to NRTIsR01GM104198 · NIGMS · UNIVERSITY OF ROCHESTER · PI KIM, BAEK · 2012 to 2018
$2.3MModulation of BAK in Lung Cancer TherapeuticsR01CA200905 · NCI · EMORY UNIVERSITY · PI DENG, XINGMING · 2017 to 2021
$1.8MModulation of Bcl2 BH4 and mTOR in lung cancer therapeuticsR01CA193828 · NCI · EMORY UNIVERSITY · PI DENG, XINGMING · 2015 to 2019
$1.8MSingle-Molecule Studies of Non-Homologous DNA End JoiningR01GM108119 · NIGMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ROTHENBERG, ELI · 2015 to 2019
$1.7MSingle-molecule studies of BRCA1-BACH1 mechanism in genomic integrityR21CA187612 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ROTHENBERG, ELI · 2015 to 2016
$451kFunctions of SAMHD1 in DNA Double-strand Break RepairF32GM121071 · NIGMS · EMORY UNIVERSITY · PI DADDACHA, WAAQO BORU · 2016 to 2016
$56kNCATS NIH HHS UL1 TR001863NCI NIH HHS R01 CA136534NCI NIH HHS R01 CA160771NCI NIH HHS R01 CA178999NCI NIH HHS R01 CA193828NCI NIH HHS R01 CA200905NCI NIH HHS R21 CA187612NIAID NIH HHS R01 AI049781NIGMS NIH HHS F32 GM121071NIGMS NIH HHS R01 GM104198NIGMS NIH HHS R01 GM108119
Abstract
DNA double-strand break (DSB) repair by homologous recombination (HR) is initiated by CtIP/MRN-mediated DNA end resection to maintain genome integrity. SAMHD1 is a dNTP triphosphohydrolase, which restricts HIV-1 infection, and mutations are associated with Aicardi-Goutières syndrome and cancer. We show that SAMHD1 has a dNTPase-independent function in promoting DNA end resection to facilitate DSB repair by HR. SAMHD1 deficiency or Vpx-mediated degradation causes hypersensitivity to DSB-inducing agents, and SAMHD1 is recruited to DSBs. SAMHD1 complexes with CtIP via a conserved C-terminal domain and recruits CtIP to DSBs to facilitate end resection and HR. Significantly, a cancer-associated mutant with impaired CtIP interaction, but not dNTPase-inactive SAMHD1, fails to rescue the end resection impairment of SAMHD1 depletion. Our findings define a dNTPase-independent function for SAMHD1 in HR-mediated DSB repair by facilitating CtIP accrual to promote DNA end resection, providing insight into how SAMHD1 promotes genome integrity.
Indexed as
DNA End-Joining RepairHomologous RecombinationDNA Breaks, Double-StrandedHCT116 CellsHEK293 CellsHeLa CellsHumansMCF-7 CellsSAM Domain and HD Domain-Containing Protein 1TransfectionSAM Domain and HD Domain-Containing Protein 1SAMHD1 protein, humanAGSautoimmuneCLLCtIPDNA damage responseDNA end resectionDNA repairdNTPHIVhomologous recombination
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