Crossover recombination is essential for homolog segregation during meiosis. In contrast to spont... more Crossover recombination is essential for homolog segregation during meiosis. In contrast to spontaneous mitotic recombination, meiotic recombination is intrinsic being initiated by the programmed formation of DNA double-strand-breaks. In addition, the tendencies of the core recombination machinery to utilize a sister-chromatid template and to produce a noncrossover outcome are counteracted by meiosis-specific factors, which ultimately ensure the formation of at least one crossover per homolog.
We identify a novel meiotic recombination intermediate, the single-end invasion (SEI), which occu... more We identify a novel meiotic recombination intermediate, the single-end invasion (SEI), which occurs during the transition from double-strand breaks (DSBs) to double-Holliday junction (dHJs). SEIs are products of strand exchange between one DSB end and its homolog. The structural asymmetry of SEIs indicates that the two ends of a DSB interact with the homolog in temporal succession, via structurally (and thus biochemically) distinct processes. SEIs arise surprisingly late in prophase, concomitant with synaptonemal complex (SC) formation. These and other data imply that SEIs are preceded by nascent DSB-partner intermediates, which then undergo selective differentiation into crossover and noncrossover types, with SC formation and strand exchange as downstream consequences. Late occurrence of strand exchange provides opportunity to reverse recombinational fate even after homologs are coaligned and/or synapsed. This feature can explain crossover suppression between homeologous and structurally heterozygous chromosomes.
Crossovers produced by homologous recombination promote accurate chromosome segregation in meiosi... more Crossovers produced by homologous recombination promote accurate chromosome segregation in meiosis and are controlled such that at least one forms per chromosome pair and multiple crossovers are widely spaced. Recombination initiates with an excess number of double-strand breaks made by Spo11 protein. Thus, crossover control involves a decision by which some breaks give crossovers while others follow a predominantly noncrossover pathway(s). To understand this decision, we examined recombination when breaks are reduced in yeast spo11 hypomorphs. We find that crossover levels tend to be maintained at the expense of noncrossovers and that genomic loci differ in expression of this "crossover homeostasis." These findings define a previously unsuspected manifestation of crossover control, i.e., that the crossover/noncrossover ratio can change to maintain crossovers. Our results distinguish between existing models of crossover control and support the hypothesis that an obligate crossover is a genetically programmed event tied to crossover interference.
Analysis of meiotic recombination by functional genomic approaches reveals prominent spatial and ... more Analysis of meiotic recombination by functional genomic approaches reveals prominent spatial and functional interactions among diverse organizational determinants. Recombination occurs between chromatin loop sequences; however, these sequences are spatially tethered to underlying chromosome axes via their recombinosomes. Meiotic chromosomal protein, Red1, localizes to chromosome axes; however, Red1 loading is modulated by R/G-bands isochores and thus by bulk chromatin state. Recombination is also modulated by isochore determinants: R-bands differentially favor double-strand break (DSB) formation but disfavor subsequent loading of meiotic RecA homolog, Dmc1. Red1 promotes DSB formation in both R- and G-bands and then promotes Dmc1 loading, specifically counteracting disfavoring R-band effects. These complexities are discussed in the context of chiasma formation as a series of coordinated local changes at the DNA and chromosome-axis levels.
Crossover recombination is essential for homolog segregation during meiosis. In contrast to spont... more Crossover recombination is essential for homolog segregation during meiosis. In contrast to spontaneous mitotic recombination, meiotic recombination is intrinsic being initiated by the programmed formation of DNA double-strand-breaks. In addition, the tendencies of the core recombination machinery to utilize a sister-chromatid template and to produce a noncrossover outcome are counteracted by meiosis-specific factors, which ultimately ensure the formation of at least one crossover per homolog.
We identify a novel meiotic recombination intermediate, the single-end invasion (SEI), which occu... more We identify a novel meiotic recombination intermediate, the single-end invasion (SEI), which occurs during the transition from double-strand breaks (DSBs) to double-Holliday junction (dHJs). SEIs are products of strand exchange between one DSB end and its homolog. The structural asymmetry of SEIs indicates that the two ends of a DSB interact with the homolog in temporal succession, via structurally (and thus biochemically) distinct processes. SEIs arise surprisingly late in prophase, concomitant with synaptonemal complex (SC) formation. These and other data imply that SEIs are preceded by nascent DSB-partner intermediates, which then undergo selective differentiation into crossover and noncrossover types, with SC formation and strand exchange as downstream consequences. Late occurrence of strand exchange provides opportunity to reverse recombinational fate even after homologs are coaligned and/or synapsed. This feature can explain crossover suppression between homeologous and structurally heterozygous chromosomes.
Crossovers produced by homologous recombination promote accurate chromosome segregation in meiosi... more Crossovers produced by homologous recombination promote accurate chromosome segregation in meiosis and are controlled such that at least one forms per chromosome pair and multiple crossovers are widely spaced. Recombination initiates with an excess number of double-strand breaks made by Spo11 protein. Thus, crossover control involves a decision by which some breaks give crossovers while others follow a predominantly noncrossover pathway(s). To understand this decision, we examined recombination when breaks are reduced in yeast spo11 hypomorphs. We find that crossover levels tend to be maintained at the expense of noncrossovers and that genomic loci differ in expression of this "crossover homeostasis." These findings define a previously unsuspected manifestation of crossover control, i.e., that the crossover/noncrossover ratio can change to maintain crossovers. Our results distinguish between existing models of crossover control and support the hypothesis that an obligate crossover is a genetically programmed event tied to crossover interference.
Analysis of meiotic recombination by functional genomic approaches reveals prominent spatial and ... more Analysis of meiotic recombination by functional genomic approaches reveals prominent spatial and functional interactions among diverse organizational determinants. Recombination occurs between chromatin loop sequences; however, these sequences are spatially tethered to underlying chromosome axes via their recombinosomes. Meiotic chromosomal protein, Red1, localizes to chromosome axes; however, Red1 loading is modulated by R/G-bands isochores and thus by bulk chromatin state. Recombination is also modulated by isochore determinants: R-bands differentially favor double-strand break (DSB) formation but disfavor subsequent loading of meiotic RecA homolog, Dmc1. Red1 promotes DSB formation in both R- and G-bands and then promotes Dmc1 loading, specifically counteracting disfavoring R-band effects. These complexities are discussed in the context of chiasma formation as a series of coordinated local changes at the DNA and chromosome-axis levels.
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Papers by Neil Hunter