ArticleProceedings of the National Academy of Sciences of the United States of America2020
CtIP promotes the motor activity of DNA2 to accelerate long-range DNA end resection.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 78 citations in OpenAlex.
- Mechanisms and disease relevance of DNA break repair pathway choice.Nature reviews. Molecular cell biology · 2026Review
- Interfering with DNA repair pathways to enhance CRISPR-Cas9-mediated homology-directed repair in a chelicerate genetic model.iScience · 2026Article
- Overcoming Resistance to PARP Inhibitors in BRCA-Mutated Cancers: Mechanisms and Therapeutic Strategies.Journal of Cancer · 2026Review
- The histone chaperone CAF-1 prevents homologous recombination-mediated instability of the budding yeast ribosomal DNA during replication-coupled DNA double-strand break repair.Nucleic acids research · 2025Article
- Mechanisms and regulation of DNA end resection in the maintenance of genome stability.Nature reviews. Molecular cell biology · 2025Review
- Using the safety scissors: DNA resection regulation at DNA double-strand breaks and telomeres.DNA repair · 2025Review
- ZNF280A links DNA double-strand break repair to human 22q11.2 distal deletion syndrome.Nature cell biology · 2025Article
- EXO1 promotes the meiotic MLH1-MLH3 endonuclease through conserved interactions with MLH1, MSH4 and DNA.Nature communications · 2025Article
- Mouse MRE11-RAD50-NBS1 is needed to start and extend meiotic DNA end resection.Nature communications · 2025Article
- Review
- Targeting BRCA1-deficient PARP inhibitor-resistant cells with nickases reveals nick resection as a cancer vulnerability.Nature cancer · 2025Article
- Article
- The Fanconi anemia core complex promotes CtIP-dependent end resection to drive homologous recombination at DNA double-strand breaks.Nature communications · 2024Article
- Helicase HELQ: Molecular Characters Fit for DSB Repair Function.International journal of molecular sciences · 2024Review
- ATM and 53BP1 regulate alternative end joining-mediated V(D)J recombination.Science advances · 2024Article
- Regulation of Precise DNA Repair by Nuclear Actin Polymerization: A Chance for Improving Gene Therapy?Cells · 2024Review
- Article
- Mechanism of DNA unwinding by MCM8-9 in complex with HROB.Nature communications · 2024Article
- Resection of DNA double-strand breaks activates Mre11-Rad50-Nbs1- and Rad9-Hus1-Rad1-dependent mechanisms that redundantly promote ATR checkpoint activation and end processing in Xenopus egg extracts.Nucleic acids research · 2024Article
- RAD51 and Infertility: A Review and Case-Control Study.Biochemical genetics · 2024Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To repair a DNA double-strand break by homologous recombination, 5'-terminated DNA strands must first be resected to reveal 3'-overhangs. This process is initiated by a short-range resection catalyzed by MRE11-RAD50-NBS1 (MRN) stimulated by CtIP, which is followed by a long-range step involving EXO1 or DNA2 nuclease. DNA2 is a bifunctional enzyme that contains both single-stranded DNA (ssDNA)-specific nuclease and motor activities. Upon DNA unwinding by Bloom (BLM) or Werner (WRN) helicase, RPA directs the DNA2 nuclease to degrade the 5'-strand. RPA bound to ssDNA also represents a barrier, explaining the need for the motor activity of DNA2 to displace RPA prior to resection. Using ensemble and single-molecule biochemistry, we show that CtIP also dramatically stimulates the adenosine 5'-triphosphate (ATP) hydrolysis-driven motor activity of DNA2 involved in the long-range resection step. This activation in turn strongly promotes the degradation of RPA-coated ssDNA by DNA2. Accordingly, the stimulatory effect of CtIP is only observed with wild-type DNA2, but not the helicase-deficient variant. Similarly to the function of CtIP to promote MRN, also the DNA2 stimulatory effect is facilitated by CtIP phosphorylation. The domain of CtIP required to promote DNA2 is located in the central region lacking in lower eukaryotes and is fully separable from domains involved in the stimulation of MRN. These results establish how CtIP couples both MRE11-dependent short-range and DNA2-dependent long-range resection and define the involvement of the motor activity of DNA2 in this process. Our data might help explain the less severe resection defects of MRE11 nuclease-deficient cells compared to those lacking CtIP.
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