Wild-Type Levels of Spo11-Induced DSBs Are Required for Normal Single-Strand Resection during Meiosis

Neale, Matthew J.; Ramachandran, Madhu; Trelles-Sticken, Edgar; Scherthan, Harry; Goldman, Alastair S. H.

doi:10.1016/s1097-2765(02)00498-7

Cited by 60 publications

(101 citation statements)

References 54 publications

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“…HindIII-alone digests are probed with a fragment (probe 2) that hybridizes to the insert loci and to the native ARG4 locus on chromosome VIII; this latter signal serves as a loading control (LC). cleaved by 7 hr after initiation of sporulation ( Figure 2A), consistent with previous reports that VDE cuts very effectively (Johnson et al, 2007;Neale et al, 2002;Terentyev et al, 2010). Thus, in most cells, both sister chromatids are cut by VDE (Gimble and Thorner, 1992;Neale et al, 2002).…”

Section: Resultssupporting

confidence: 91%

“…While VDEDSBs form at similar levels and timing in SPO11 and spo11 mutant cells (Johnson et al, 2007;Neale et al, 2002;Terentyev et al, 2010), features of VDE-DSB repair, including the extent of end Figure 2C at HIS4 (top) and Figure 4 continued on next page resection, are strongly influenced by the presence or absence of Spo11-DSBs (Neale et al, 2002). To determine if other aspects of VDE-initiated recombination are also affected, we examined VDEinitiated recombination in a catalysis-null spo11-Y135F mutant, hereafter called spo11.…”

Section: Spo11-dsbs Promote Vde-initiated Mutlg-dependent Cosmentioning

confidence: 99%

“…To account for the reduced levels and MutLg-independence of VDE-initiated COs in spo11 mutants, we suggest that a single VDE-DSB is not sufficient to promote stable homolog pairing, and that additional DSBs along a chromosome are needed to promote stable homolog pairing, which in turn is needed to form ZMM protein-containing structures that stabilize JMs and recruit MutLg. However, the 140-190 Spo11-DSBs that form in each meiotic cell (Buhler et al, 2007) are also expected to induce a nucleus-wide DNA damage-response, and to compete with other DSBs for repair activities whose availability is limited, and both have the potential to alter recombination biochemistry at VDE-DSBs (Johnson et al, 2007;Neale et al, 2002). Thus, while we believe it likely that defects in homolog pairing and synapsis are responsible for the observed impact of spo11 mutation on VDE-initiated CO formation, it remains possible that it is due to changes in DNA damage signaling, repair protein availability, or in other processes that are affected by global Spo11-DSB levels.…”

Section: The Interplay Of Resolvase Activities Is Chromosome Context-mentioning

confidence: 99%

“…VDE-catalyzed DSBs (hereafter called VDE-DSBs) form independent of Spo11 and meiotic axis proteins. However, like Spo11-DSBs, VDE-DSBs form after pre-meiotic DNA replication and are repaired using end-processing and strand invasion activities that also repair Spo11-DSBs (Fukuda et al, 2003;Neale et al, 2002). We examined resolvase contributions to VDE-initiated CO formation, and obtained evidence that local enrichment for meiotic axis proteins promotes MutLg-dependent CO formation; while recombination that occurs outside of this specialized environment forms COs by MutLg-independent mechanisms.…”

Section: Introductionmentioning

confidence: 99%

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Local chromosome context is a major determinant of crossover pathway biochemistry during budding yeast meiosis

Medhi¹,

Goldman

Lichten³

2016

Preprint

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The budding yeast genome contains regions where meiotic recombination initiates more frequently than in others. This pattern parallels enrichment for the meiotic chromosome axis proteins Hop1 and Red1. These proteins are important for Spo11-catalyzed double strand break formation; their contribution to crossover recombination remains undefined. Using the sequencespecific VMA1-derived endonuclease (VDE) to initiate recombination in meiosis, we show that chromosome structure influences the choice of proteins that resolve recombination intermediates to form crossovers. At a Hop1-enriched locus, most VDE-initiated crossovers, like most Spo11-initiated crossovers, required the meiosis-specific MutLg resolvase. In contrast, at a locus with lower Hop1 occupancy, most VDE-initiated crossovers were MutLg-independent. In pch2 mutants, the two loci displayed similar Hop1 occupancy levels, and VDE-induced crossovers were similarly MutLg-dependent. We suggest that meiotic and mitotic recombination pathways coexist within meiotic cells, and that features of meiotic chromosome structure determine whether one or the other predominates in different regions.

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Section: Resultssupporting

confidence: 91%

Section: Spo11-dsbs Promote Vde-initiated Mutlg-dependent Cosmentioning

confidence: 99%

Section: The Interplay Of Resolvase Activities Is Chromosome Context-mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Local chromosome context is a major determinant of crossover pathway biochemistry during budding yeast meiosis

Medhi¹,

Goldman

Lichten³

2016

Preprint

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“…Rec12 (Spo11) protein itself may have a role in the choice of which resolution pathway is used: In budding yeast Spo11 affects resection from double-strand DNA breaks and the length of resulting 3′ single-stranded DNA ends, which may influence subsequent pathway choice (Neale et al, 2002). In fission yeast rec12-D15 (null) mutants lack both crossover and noncrossover recombination (Sharif et al, 2002), but the rec12-117 allele was hypothesized to affect differentially (by a factor of ≥25) the choice of recombination pathways (DeVeaux et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

A DNA binding motif of meiotic recombinase Rec12 (Spo11) defined by essential glycine-202, and persistence of Rec12 protein after completion of recombination

DeWall¹,

Davidson²,

Sharif³

et al. 2005

Gene

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The Rec12 (Spo11) protein of the fission yeast Schizosaccharomyces pombe is a meiosis-specific ortholog of the catalytic subunit of type VI topoisomerases and is thought to catalyze doublestrand DNA breaks that initiate recombination. We tested the hypothesis that the rec12-117 allele affects the choice of pathways by which recombination is resolved. DNA sequence analysis revealed a single missense mutation in the coding region (rec12-G202E). The corresponding glycine-202 residue of Rec12 protein is strictly conserved in proteins of the Rec12/Spo11/Top6A family. It maps to the base of the DNA binding pocket in the crystal structure of the archaeal ortholog, Top6A. The rec12-G202E mutants lacked crossover and non-crossover recombination, demonstrating that rec12-G202E does not affect choice of resolution pathway. Like rec12-D15 null mutants, the rec12-G202E mutants suffered chromosome segregation errors in meiosis I. The Rec12-G202E protein was as stable as wild-type Rec12, demonstrating that glycine-202 is essential for a biochemical activity of Rec12 protein, rather than for its stability. These findings suggest that Rec12 facilitates binding of the meiotic recombinase to its substrate, DNA. Interestingly, the bulk of Rec12 protein persisted until the time of anaphase I, and a portion of Rec12 protein persisted until the time of anaphase II, after which it was undetectable. This suggests that Rec12 protein has additional meiotic functions after completion of recombination in prophase, as inferred previously from genetic studies.

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Spo11 and the Formation of DNA Double-Strand Breaks in Meiosis

Keeney

Genome Dynamics and Stability

311

359

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Meiotic recombination is carried out through a specialized pathway for the formation and repair of DNA double-strand breaks made by the Spo11 protein, a relative of archaeal topoisomerase VI. This review summarizes recent studies that provide insight to the mechanism of DNA cleavage by Spo11, functional interactions of Spo11 with other proteins required for break formation, mechanisms that control the timing of recombination initiation, and evolutionary conservation and divergence of these processes.

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Wild-Type Levels of Spo11-Induced DSBs Are Required for Normal Single-Strand Resection during Meiosis

Cited by 60 publications

References 54 publications

Local chromosome context is a major determinant of crossover pathway biochemistry during budding yeast meiosis

Local chromosome context is a major determinant of crossover pathway biochemistry during budding yeast meiosis

A DNA binding motif of meiotic recombinase Rec12 (Spo11) defined by essential glycine-202, and persistence of Rec12 protein after completion of recombination

Spo11 and the Formation of DNA Double-Strand Breaks in Meiosis

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