Meiosis-Specific DNA Double-Strand Breaks Are Catalyzed by Spo11, a Member of a Widely Conserved Protein Family

@article{Keeney1997MeiosisSpecificDD,
  title={Meiosis-Specific DNA Double-Strand Breaks Are Catalyzed by Spo11, a Member of a Widely Conserved Protein Family},
  author={S. Keeney and C. Giroux and N. Kleckner},
  journal={Cell},
  year={1997},
  volume={88},
  pages={375-384}
}
Meiotic recombination in S. cerevisiae is initiated by double-strand breaks (DSBs). In certain mutants, breaks accumulate with a covalently attached protein, suggesting that cleavage is catalyzed by the DSB-associated protein via a topoisomerase-like transesterase mechanism. We have purified these protein-DNA complexes and identified the protein as Spo11, one of several proteins required for DSB formation. These findings strongly implicate Spo11 as the catalytic subunit of the meiotic DNA… Expand
Both conserved and non-conserved regions of Spo11 are essential for meiotic recombination initiation in yeast
TLDR
Analysis of mutation sites of isolated spo11-mutant alleles indicated that both N-terminal and C-Terminal non-conserved residues of Spo11 are essential for the protein’s function, possibly for interaction with other meiotic DSB enzymes. Expand
Identification of Residues in Yeast Spo11p Critical for Meiotic DNA Double-Strand Break Formation
TLDR
Results are consistent with a multimeric structure for Spo11p in vivo but may also indicate that the amount of Spo11 protein is not a limiting factor for DSB formation in normal cells. Expand
A DNA topoisomerase VI–like complex initiates meiotic recombination
TLDR
Findings suggest that the catalytic core complex responsible for meiotic DSB formation in eukaryotes adopts a topo VI–like structure. Expand
Functional characterization of the meiosis-specific DNA double-strand break inducing factor SPO-11 from C. elegans
The programmed induction of meiotic DNA double-strand breaks (DSBs) by the evolutionarily conserved SPO-11 protein, which is structurally related to archaeal Topo VIA topoisomerases, triggers meioticExpand
[SPO11: an activity that promotes DNA breaks required for meiosis].
TLDR
Similarities and differences from species to species uncover a complex set of regulations that coordinate recombination with other events of meiotic prophase, such as chromosome pairing and meiotic cell cycle. Expand
A new light on the meiotic DSB catalytic complex.
TLDR
An overview of the knowledge on TopoVI structure and mode of action is provided and they are compared with their meiotic counterparts to discuss the nature, structure and functions of the meiotic Topo VI-like complex during meiotic DSB formation. Expand
The TopoVIB-Like protein family is required for meiotic DNA double-strand break formation
TLDR
It is concluded that meiotic DSBs are catalyzed by a complex involving SPO11 and TOPOVIBL, and a conserved family of plant and animal proteins that share strong structural similarity to the TopoVIB subunit of TopoVI DNA topoisomerase are identified. Expand
Replication protein A is required for meiotic recombination in Saccharomyces cerevisiae.
TLDR
A study of the meiotic phenotypes conferred by two missense mutations affecting the largest subunit of RPA, which are localized in the protein interaction domain (rfa1-t11 and in the DNA-binding domain) and find that both mutant diploids exhibit reduced sporulation efficiency, very poor spore viability, and a 10- to 100-fold decrease in meiotic recombination. Expand
Functional conservation of Mei4 for meiotic DNA double-strand break formation from yeasts to mice.
TLDR
It is proposed that Mei4 acts as a structural component of the DSB machinery that ensures meiotic DSB formation on chromosome axes, and it is shown that mouse MEI4 and REC114 proteins interact directly, and conserved motifs are identified as required for this interaction. Expand
Endonucleolytic processing of covalent protein-linked DNA double-strand breaks
TLDR
It is shown that meiotic DSBs in budding yeast are processed by endonucleolytic cleavage that releases Spo11 attached to an oligonucleotide with a free 3′-OH, indicating that the ends of a single DSB may be biochemically distinct at or before the initial processing step—much earlier than previously thought. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 106 REFERENCES
Covalent protein-DNA complexes at the 5' strand termini of meiosis-specific double-strand breaks in yeast.
  • S. Keeney, N. Kleckner
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1995
TLDR
It is proposed that the DSB-associated protein is the catalytic subunit of the meiotic recombination initiation nuclease and that it cleaves DNA via a covalent protein-DNA intermediate. Expand
Isolation of COM1, a new gene required to complete meiotic double-strand break-induced recombination in Saccharomyces cerevisiae.
TLDR
A mutation com1-1 is identified, which blocks processing of meiotic double-strand breaks and which interferes with synaptonemal complex formation, homologous pairing and, as a consequence, spore viability after induction ofmeiotic recombination. Expand
DMC1: A meiosis-specific yeast homolog of E. coli recA required for recombination, synaptonemal complex formation, and cell cycle progression
TLDR
DMC1 phenotypes provide further evidence that recombination and SC formation are interrelated processes and are consistent with a requirement for DNA-DNA interactions during SC formation, and additional evidence suggests that arrest occurs at a meiosis-specific cell cycle "checkpoint" in response to a primary defect in prophase chromosome metabolism. Expand
A pathway for generation and processing of double-strand breaks during meiotic recombination in S. cerevisiae
We have identified and analyzed a meiotic reciprocal recombination hot spot in S. cerevisiae. We find that double-strand breaks occur at two specific sites associated with the hot spot and thatExpand
The role of the SPO11 gene in meiotic recombination in yeast.
TLDR
The SPO11 gene is specifically required for meiotic recombination and the Rec- meiotic defect conferred by spo11-1 was confirmed by dyad analysis of spores derived from spo13-1 single-division meiosis in which recombination is not a requirement for viable ascospore production. Expand
The yeast MER2 gene is required for chromosome synapsis and the initiation of meiotic recombination.
TLDR
The results of a physical assay demonstrate that the mer2 mutation prevents the formation of meiosis-specific, double-strand breaks, indicating that the Mer2 protein acts at or before the initiation of meiotic recombination. Expand
The nucleotide mapping of DNA double‐strand breaks at the CYS3 initiation site of meiotic recombination in Saccharomyces cerevisiae.
TLDR
A model for the initiation of meiotic recombination is presented taking into account the implications of these results, which show that the activity involved in DSB formation has little or no sequence specificity. Expand
Interaction of Mre11 and Rad50: two proteins required for DNA repair and meiosis-specific double-strand break formation in Saccharomyces cerevisiae.
TLDR
Characterization of two double mutants showed that MRE11 and RAD50 belong to the same epistasis group with respect to meiotic DSB formation and mitotic DNA repair, and using a two-hybrid system, it is found that Mre11 interacts with Rad50 and itself in vivo. Expand
Analysis of wild-type and rad50 mutants of yeast suggests an intimate relationship between meiotic chromosome synapsis and recombination
TLDR
The meiotic and mitotic defects of rad50 mutants can be accounted for economically by the proposal that meiotic recombination, meiotic chromosome pairing, and vegetative DNA repair all use a common chromosomal homology search that involves RAD50 function. Expand
The location and structure of double‐strand DNA breaks induced during yeast meiosis: evidence for a covalently linked DNA‐protein intermediate.
TLDR
It is suggested that, in S.cerevisiae, meiotic recombination is initiated by a DSB‐forming activity that creates a covalently linked protein‐DNA intermediate that leads to double‐strand DNA breaks formed during meiosis. Expand
...
1
2
3
4
5
...