ArticleScience (New York, N.Y.)2025
CTC1-STN1-TEN1 controls DNA break repair pathway choice via DNA end resection blockade.
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Article in Science (New York, N.Y.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11citing papers in PubMed
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Who cites it
11 citing papers in PubMed.
- Mechanisms and disease relevance of DNA break repair pathway choice.Nature reviews. Molecular cell biology · 2026Review
- STN1 upregulation promotes PARPi resistance in BRCA2-deficient cancer cells via replication fork protection and suppression of ssDNA gap formation.NAR cancer · 2026Article
- CST complex promotes second-strand synthesis in break-induced replication.Nature structural & molecular biology · 2026Article
- STN1 upregulation promotes PARPi resistance in BRCA2-deficient cancer cells via replication fork protection and suppression of ssDNA gap formation.bioRxiv : the preprint server for biology · 2026Article
- 53BP1-independent Shieldin-BRCA1 antagonism at replication-coupled double-strand breaks.Nature communications · 2026Article
- Interplay Between Poly(ADP-ribosyl)ation and Specific Inner Cellular Events That Suggest Combination Strategies for Overcoming PARP Inhibitor Resistance.Pharmaceutics · 2026Review
- Identification of novelTherapeutic advances in hematology · 2026Article
- Plant tolerance mechanisms to DNA-damaging UV stress.Journal of experimental botany · 2025Review
- Stn1 supports Mec1 function in protecting stalled replication forks from degradation.PLoS genetics · 2025Article
- Using the safety scissors: DNA resection regulation at DNA double-strand breaks and telomeres.DNA repair · 2025Review
- CTC1-STN1-TEN1 controls DNA break repair pathway choice via DNA end resection blockade.Science (New York, N.Y.) · 2025Article
Corrections and comments
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Authors and funding
32 authors.
Cody M Rogers *Department of Biochemistry and Structural Biology and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.ORCID 0000-0001-6499-1390
Hardeep Kaur *Department of Biochemistry and Structural Biology and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.ORCID 0000-0002-6385-8413
Michelle L Swift *Division of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-3645-1308
Vivek B RainaDepartment of Biochemistry and Molecular Biophysics, Columbia University Irving Medical Center, New York, NY, USA.ORCID 0000-0003-0507-9208
Shuo ZhouDepartment of Biochemistry and Structural Biology and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.ORCID 0000-0001-8684-8341
Ajinkya S KawaleDepartment of Biochemistry and Structural Biology and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.ORCID 0000-0001-7154-2868
Shahrez SyedDepartment of Biochemistry and Structural Biology and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.ORCID 0000-0002-0491-3566
Korilynn G KellyDepartment of Biochemistry and Structural Biology and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.ORCID 0009-0002-4781-7141
Angela M JasperDepartment of Biochemistry and Structural Biology and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.ORCID 0000-0002-9548-8445
Sameer SalunkheDepartment of Biochemistry and Structural Biology and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Youngho KwonDepartment of Biochemistry and Structural Biology and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.ORCID 0000-0002-0287-8795
Jeffrey WangDepartment of Biochemistry and Structural Biology and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.ORCID 0000-0002-5376-1001
Aida Badamchi ShabestariDepartment of Biochemistry and Structural Biology and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
James M DaleyDepartment of Biochemistry and Structural Biology and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Adam SacksDepartment of Biochemistry and Structural Biology and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.ORCID 0000-0001-7621-3801
Maria E GaczynskaDepartment of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.ORCID 0000-0002-9033-5706
Pawel A OsmulskiDepartment of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.ORCID 0000-0002-5359-9200
Yashpal RawalDepartment of Biochemistry and Structural Biology and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.ORCID 0000-0001-9209-788X
Nozomi TomimatsuDepartment of Neurosurgery, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Simon A GaytherDepartment of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Kate LawrensonDepartment of Obstetrics and Gynecology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Sandeep BurmaDepartment of Biochemistry and Structural Biology and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Elizabeth V WasmuthDepartment of Biochemistry and Structural Biology and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.ORCID 0000-0003-1474-4935
Shaun K OlsenDepartment of Biochemistry and Structural Biology and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.ORCID 0000-0002-1265-7101
Weixing ZhaoDepartment of Biochemistry and Structural Biology and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.ORCID 0000-0001-5746-3696
Robert HromasDepartment of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.ORCID 0000-0002-1916-6276
David S LibichDepartment of Biochemistry and Structural Biology and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.ORCID 0000-0001-6492-2803
Alexander V MazinDepartment of Biochemistry and Structural Biology and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.ORCID 0000-0002-5430-9797
Daohong ZhouDepartment of Biochemistry and Structural Biology and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Eric C GreeneDepartment of Biochemistry and Molecular Biophysics, Columbia University Irving Medical Center, New York, NY, USA.ORCID 0000-0002-7387-824X
Dipanjan ChowdhuryDivision of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-5645-3752
Patrick SungDepartment of Biochemistry and Structural Biology and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.ORCID 0000-0003-1396-9040
Funding
Transcription-Coupled & Replication-Associated Excision RepairP01CA092584 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI WALTER J. CHAZIN · 2001 to 2026
$89.6MTISSUE CULTURE---COREP30CA054174 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Robin Jean Leach · 1991 to 2026
$59.1MTRAINING GRANT ON THE BIOLOGY OF AGINGT32AG021890 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Erzsebet Kokovay, JAMES FLOYD NELSON · 2003 to 2026
$11.4MRegulation of BRCA-dependent Genome Repair via the 53BP1 AxisP01CA275717 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Patrick Sung · 2024 to 2026
$10.1MYEAST DNA REPAIR GENES AND PROTEINS OF THE RAD52 GROUPR01ES007061 · NIEHS · YALE UNIVERSITY · PI Patrick Sung · 1995 to 2026
$9.4MMechanisms of DNA Homology-directed Genome Repair and Tumor SuppressionR35CA241801 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI SUNG, PATRICK · 2019 to 2025
$6.0MMechanistic Dissection of the Fanconi Anemia Pathway of DNA Damage Response and RR01CA168635 · NCI · YALE UNIVERSITY · PI Gary M Kupfer, Patrick Sung · 2013 to 2026
$5.8MProtein purification instrumentation in support of single molecule studies of genome integrityR35GM118026 · NIGMS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GREENE, ERIC C · 2016 to 2025
$5.7MCharacterizing non-coding somatic and germline variant interactions in ovarian cancerR01CA244569 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI GAYTHER, SIMON ANDREW, GUSEV, ALEXANDER · 2020 to 2024
$3.3MCancer Biology Training ProgramT32CA148724 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Pei Wang, Feng-Chun Yang · 2011 to 2026
$3.3MEEPD1 Repair of Stressed Replication ForksR01CA205224 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Robert A Hromas · 2016 to 2026
$3.3MAML mutation-guided drugging of DNA repairR01CA237286 · NCI · TEMPLE UNIV OF THE COMMONWEALTH · PI MAZIN, ALEXANDER V, SKORSKI, TOMASZ · 2020 to 2024
$2.8MNCI NIH HHS F30 CA278370NCI NIH HHS P01 CA092584NCI NIH HHS P01 CA275717NCI NIH HHS P30 CA054174NCI NIH HHS R01 CA168635NCI NIH HHS R01 CA205224NCI NIH HHS R01 CA236606NCI NIH HHS R01 CA237286NCI NIH HHS R01 CA244569NCI NIH HHS R01 CA246807NCI NIH HHS R01 CA264900NCI NIH HHS R01 CA268641NCI NIH HHS R01 CA293655NCI NIH HHS R35 CA241801NCI NIH HHS R50 CA265315NCI NIH HHS T32 CA148724NCI NIH HHS T32 CA279363NIA NIH HHS T32 AG021890NIEHS NIH HHS R01 ES007061NIGMS NIH HHS F32 GM149115NIGMS NIH HHS R00 GM140264NIGMS NIH HHS R01 GM136717NIGMS NIH HHS R01 GM140127NIGMS NIH HHS R01 GM141091NIGMS NIH HHS R35 GM118026NIGMS NIH HHS T32 GM145432
Abstract
Antagonistic activities of the 53BP1 axis and the tumor suppressor BRCA1-BARD1 determine whether DNA double-strand breaks (DSBs) are repaired by end joining or homologous recombination. We show that the CTC1-STN1-TEN1 (CST) complex, a central 53BP1 axis component, suppresses DNA end resection by EXO1 and the BLM-DNA2 helicase-nuclease complex but acts by distinct mechanisms in restricting these entities. Whereas BRCA1-BARD1 alleviates the CST-imposed EXO1 blockade, it has little effect on BLM-DNA2 restriction. CST mutants impaired for DNA binding or BLM-EXO1 interaction exhibit a hyper-resection phenotype and render BRCA1-deficient cells resistant to poly(ADP-ribose) polymerase (PARP) inhibitors. Our findings mechanistically define the crucial role of CST in DNA DSB repair pathway choice and have implications for understanding cancer therapy resistance stemming from dysfunction of the 53BP1 axis.
Indexed as
DNA Breaks, Double-StrandedDNA End-Joining RepairDNA RepairTelomere-Binding ProteinsBRCA1 ProteinDNA HelicasesDNA Repair EnzymesExodeoxyribonucleasesHomologous RecombinationHumansPoly(ADP-ribose) Polymerase InhibitorsRecombinational DNA RepairRecQ HelicasesTumor Suppressor p53-Binding Protein 1Tumor Suppressor ProteinsUbiquitin-Protein LigasesBloom syndrome proteinBRCA1 ProteinBRCA1 protein, humanCtc1 protein, humanDNA2 protein, humanDNA HelicasesDNA Repair EnzymesEXO1 protein, humanexodeoxyribonuclease IExodeoxyribonucleasesPoly(ADP-ribose) Polymerase InhibitorsRecQ HelicasesTelomere-Binding ProteinsTP53BP1 protein, humanTumor Suppressor p53-Binding Protein 1Tumor Suppressor ProteinsUbiquitin-Protein Ligases
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