Endonucleolytic processing of covalent protein-linked DNA double-strand breaks
By Matthew J. Neale, Jing Pan, Scott Keeney. Nature, 2005
608 citations recorded by the source corpus.
DNA double-strand breaks (DSBs) with protein covalently attached to 5′ strand termini are formed by Spo11 to initiate meiotic recombination. The Spo11 protein must be removed for the DSB to be repaired, but the mechanism for removal is unclear. Here we show that meiotic DSBs in budding yeast are processed by endonucleolytic cleavage that releases Spo11 attached to an oligonucleotide with a free 3′-OH. Two discrete Spo11–oligonucleotide complexes were found in equal amounts, differing with respect to the length of the bound DNA. We propose that these forms arise from different spacings of strand cleavages flanking the DSB, with every DSB processed asymmetrically. Thus, the ends of a single DSB may be biochemically distinct at or before the initial processing step—much earlier than previously thought. SPO11–oligonucleotide complexes were identified in extracts of mouse testis, indicating that this mechanism is evolutionarily conserved. Oligonucleotide–topoisomerase II complexes were also present in extracts of vegetative yeast, although not subject to the same genetic control as for generating Spo11–oligonucleotide complexes. Our findings suggest a general mechanism for repair of protein-linked DSBs.
Subfields: Cell Biology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/1423d8469726c223894383c819b78f506c0b60af
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In Cell Biology
In Molecular Biology
- Rodney Rothstein
- M. Jasin
- Jacob C. Harrison
- J. R. Chapman
- J. Haber
- S. Boulton
- Martin R. G. Taylor
- J. Petrini
Citations in the corpus
- Surviving the breakup: the DNA damage checkpoint. (2006, background): “The MRX complex appears to be regulated by the Sae2 protein, and deletion of Sae2 phenocopies specific mutations in Rad50 and Mre11 called rad50-S and mre11-S (15, 93, 98, 104, 114).”
- The MRE11 complex: starting from the ends (2011, background): “The Mre11 complex subsequently mediates endonucleolytic removal of two differently sized Spo11–DNA oligo species, suggesting that Mre11 cleaves Spo11-bound termini asymmetricall”
- Sgs1 helicase and two nucleases Dna2 and Exo1 resect DNA double strand break ends (2008, unknown): “Mre11 nuclease activity is directly responsible for processing Spo11-induced DSBs only in meiotic cells, most likely by removing covalently bound Spo11 from DSB ends (Furuse et al., 1998; Moreau et al., 1999; Neale et al., 2005; Tsubouchi and Ogawa, 1998; Usui et al., 1998).”
- Repair of strand breaks by homologous recombination. (2013, background): “When introducing a DSB, Spo11 protein remains covalently bound to the ends before it is removed during endonucleolytic processing (Neale et al. 2005; Garcia et al. 2011).”
- Playing the end game: DNA double-strand break repair pathway choice. (2012, background): “This involves the asymmetric endonucleolytic cleavageof the50DNAendsadjacent toSpo11, resulting in the release of 10–40 bp long 50-bound Spo11-DNA oligonucleotide complexes (Neale et al., 2005).”