ArticlePLoS genetics2011
Release of Ku and MRN from DNA ends by Mre11 nuclease activity and Ctp1 is required for homologous recombination repair of double-strand breaks.
Article in PLoS genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 161 papers.
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Who cites it
161 citing papers in PubMed, 223 citations in OpenAlex.
- Mechanisms and disease relevance of DNA break repair pathway choice.Nature reviews. Molecular cell biology · 2026Review
- Activation of Pol theta-mediated end joining begins during mitotic commitment.bioRxiv : the preprint server for biology · 2026Article
- A CRISPR/Cas9-induced blunt-end telomere system in S. pombe reveals RNase H2-dependent RNA primer removal at the terminal Okazaki fragment of lagging telomeres.Nucleic acids research · 2026Article
- The LINC complex component Kms1 and CENP-B protein Cbp1 cooperate to enforce faithful homology-directed DNA repair at the nuclear periphery inGenes & development · 2026Article
- CK2-mediated HDAC5 shuttling regulates DNA end resection through Ku70 deacetylation.Theranostics · 2026Article
- The LINC complex component Kms1 and CENP-B protein Cbp1 cooperate to enforce faithful homology-directed DNA repair at the nuclear periphery inbioRxiv : the preprint server for biology · 2025Article
- Pathogenic variants in MAEA disrupt DNA replication fork stability and are associated with developmental abnormalities in humans.Science advances · 2025Article
- Ccq1 restrains Mre11-mediated degradation to distinguish short telomeres from double-strand breaks.Nucleic acids research · 2024Article
- Mechanistic insights into DNA damage recognition and checkpoint control in plants.Nature plants · 2024Review
- MRE11A: a novel negative regulator of human DNA mismatch repair.Cellular & molecular biology letters · 2024Article
- Article
- Short-range end resection requires ATAD5-mediated PCNA unloading for faithful homologous recombination.Nucleic acids research · 2023Article
- Multi-step processing of replication stress-derived nascent strand DNA gaps by MRE11 and EXO1 nucleases.Nature communications · 2023Article
- Structure and mechanism in non-homologous end joining.DNA repair · 2023Article
- Review
- PRMT1 and PRMT5: on the road of homologous recombination and non-homologous end joining.Genome instability & disease · 2023Article
- The Ku complex promotes DNA end-bridging and this function is antagonized by Tel1/ATM kinase.Nucleic acids research · 2023Article
- The Chromatin Landscape around DNA Double-Strand Breaks in Yeast and Its Influence on DNA Repair Pathway Choice.International journal of molecular sciences · 2023Review
- The mechanism and clinical application of DNA damage repair inhibitors combined with immune checkpoint inhibitors in the treatment of urologic cancer.Frontiers in cell and developmental biology · 2023Review
- High-throughput screen to identify compounds that prevent or target telomere loss in human cancer cells.NAR cancer · 2022Article
101 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The multifunctional Mre11-Rad50-Nbs1 (MRN) protein complex recruits ATM/Tel1 checkpoint kinase and CtIP/Ctp1 homologous recombination (HR) repair factor to double-strand breaks (DSBs). HR repair commences with the 5'-to-3' resection of DNA ends, generating 3' single-strand DNA (ssDNA) overhangs that bind Replication Protein A (RPA) complex, followed by Rad51 recombinase. In Saccharomyces cerevisiae, the Mre11-Rad50-Xrs2 (MRX) complex is critical for DSB resection, although the enigmatic ssDNA endonuclease activity of Mre11 and the DNA-end processing factor Sae2 (CtIP/Ctp1 ortholog) are largely unnecessary unless the resection activities of Exo1 and Sgs1-Dna2 are also eliminated. Mre11 nuclease activity and Ctp1/CtIP are essential for DSB repair in Schizosaccharomyces pombe and mammals. To investigate DNA end resection in Schizo. pombe, we adapted an assay that directly measures ssDNA formation at a defined DSB. We found that Mre11 and Ctp1 are essential for the efficient initiation of resection, consistent with their equally crucial roles in DSB repair. Exo1 is largely responsible for extended resection up to 3.1 kb from a DSB, with an activity dependent on Rqh1 (Sgs1) DNA helicase having a minor role. Despite its critical function in DSB repair, Mre11 nuclease activity is not required for resection in fission yeast. However, Mre11 nuclease and Ctp1 are required to disassociate the MRN complex and the Ku70-Ku80 nonhomologous end-joining (NHEJ) complex from DSBs, which is required for efficient RPA localization. Eliminating Ku makes Mre11 nuclease activity dispensable for MRN disassociation and RPA localization, while improving repair of a one-ended DSB formed by replication fork collapse. From these data we propose that release of the MRN complex and Ku from DNA ends by Mre11 nuclease activity and Ctp1 is a critical step required to expose ssDNA for RPA localization and ensuing HR repair.
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