ArticleNature2014
Sae2 promotes dsDNA endonuclease activity within Mre11-Rad50-Xrs2 to resect DNA breaks.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 280 papers.
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Who cites it
280 citing papers in PubMed, 443 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 Tel1-Rad9 axis links DNA double-strand break end-tethering to repair pathway choice.Nucleic acids research · 2026Article
- Crossover control: A key to unlocking genetic diversity in plant breeding.Journal of integrative plant biology · 2026Review
- R-loops and D-loops: a delicate balance in genomic stability and instability.Cell communication and signaling : CCS · 2026Review
- Rap1-mediated steric hindrance protects telomeres from MRX sensing.Nature structural & molecular biology · 2026Article
- Engineering yeast chromosomal telomeres with a bacteriophage system.Nature communications · 2026Article
- A phosphorylation switch at MRE11 links ATM-ATR and calcium signaling to safeguard stalled replication fork stability.Research square · 2026Article
- Chromatin Remodeling, DNA Double-Strand Break Repair, and Human Disease: How a Breakup Changes You.Biomolecules · 2026Review
- Sae2 integrates CDK and checkpoint phosphorylation to coordinate MRX cleavage with checkpoint attenuation.Communications biology · 2025Article
- The Converging Roles of Nucleases and Helicases in Genome Maintenance and the Aging Process.Life (Basel, Switzerland) · 2025Review
- Break-induced replication is activated to repair R-loop-associated double-strand breaks in SETX-deficient cells.Cell reports · 2025Article
- Phase separation of ERCC6L2-CtIP regulates the extent of DNA end resection.Nature cell biology · 2025Article
- Article
- Structural basis for DNA break sensing by human MRE11-RAD50-NBS1 and its regulation by telomeric factor TRF2.Nature communications · 2025Article
- Insight into meiotic DNA end resection: Mechanisms and regulation.DNA repair · 2025Review
- DNA double-strand break end resection factors and WRN facilitate mitotic DNA synthesis in human cells.Nature communications · 2025Article
- Mechanisms and regulation of DNA end resection in the maintenance of genome stability.Nature reviews. Molecular cell biology · 2025Review
- EXO1 promotes the meiotic MLH1-MLH3 endonuclease through conserved interactions with MLH1, MSH4 and DNA.Nature communications · 2025Article
- MRN-CtIP, EXO1, and DNA2-WRN/BLM act bidirectionally to process DNA gaps in PARPi-treated cells without strand cleavage.Genes & development · 2025Article
220 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To repair double-strand DNA breaks by homologous recombination, the 5'-terminated DNA strand must first be resected, which generates 3' single-stranded DNA overhangs. Genetic evidence suggests that this process is initiated by the Mre11-Rad50-Xrs2 (MRX) complex. However, its involvement was puzzling, as the complex possesses exonuclease activity with the opposite (3' to 5') polarity from that required for homologous recombination. Consequently, a bidirectional model has been proposed whereby dsDNA is first incised endonucleolytically and MRX then proceeds back to the dsDNA end using its 3' to 5' exonuclease. The endonuclease creates entry sites for Sgs1-Dna2 and/or Exo1, which then carry out long-range resection in the 5' to 3' direction. However, the identity of the endonuclease remained unclear. Using purified Saccharomyces cerevisiae proteins, we show that Sae2 promotes dsDNA-specific endonuclease activity by the Mre11 subunit within the MRX complex. The endonuclease preferentially cleaves the 5'-terminated dsDNA strand, which explains the polarity paradox. The dsDNA end clipping is strongly stimulated by protein blocks at the DNA end, and requires the ATPase activity of Rad50 and physical interactions between MRX and Sae2. Our results suggest that MRX initiates dsDNA break processing by dsDNA endonuclease rather than exonuclease activity, and that Sae2 is the key regulator of this process. These findings demonstrate a probable mechanism for the initiation of dsDNA break processing in both vegetative and meiotic cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.