Biology subjects

Heldrich, J.

Publications and source records attributed to Heldrich, J..

4 recordsLinked to original sources

bioRxiv2020

A cohesin-independent mechanism modulates recombination activity along meiotic chromosomes

Successful meiotic recombination, and thus fertility, depends on conserved axis proteins that organize chromosomes into arrays of anchored chromatin loops and provide a protected environment for DNA exchange. Here, we show that the stereotypic chromosomal distribution of axis proteins in S. cerevisiae is the additive result of two independent pathways: a cohesin-dependent pathway, which was previously identified and mediates focal enrichment of axis proteins at gene ends, and a parallel cohesin-independent pathway that recruits axis proteins to broad genomic islands with high gene density. These islands exhibit elevated markers of crossover recombination as well as increased nucleosome density, which we show is a direct consequence of the underlying DNA sequence. A predicted PHD domain in the center of the axis factor Hop1 specifically mediates cohesin-independent axis recruitment. Intriguingly, other chromosome organizers, including cohesin, condensin, and topoisomerases, are differentially depleted from the same regions even in non-meiotic cells, indicating that these DNA sequence-defined chromatin islands exert a general influence on the patterning of chromosome structure.

genomics↗

bioRxiv2020

DNA break formation induces Scc2/cohesin-dependent recruitment of condensin to meiotic chromosomes

Crossover recombination supports meiotic chromosome inheritance and fertility by establishing chiasmata between homologous chromosomes prior to the first meiotic division. In addition to the physical exchange of DNA mediated by meiotic recombination, chiasma formation also involves restructuring of the underlying chromosome axis, possibly to help with chiasma maturation or to resolve chromosomal interlocks. Here, we identify condensin as an important regulator of axis remodeling in S. cerevisiae. Condensin is recruited near sites of meiotic crossover designation by pro-crossover factors but is largely dispensable for DNA exchange. Instead, condensin helps to create discontinuities in the meiotic chromosome axis by promoting removal of cohesin. In addition, chromosomes of condensin mutants exhibit unusually common parallel chromatin clouds and experience a chromosomal buildup of the conserved axis remodeler Pch2. Consistent with an important role of axis restructuring at crossover sites, the canonical anaphase-bridge phenotype of condensin mutants is partly rescued by redirecting meiotic DNA repair to sister chromatids instead of homologous chromosomes, suggesting that crossover-associated axis reorganization is important for faithful meiotic chromosome segregation.

genomics↗

bioRxiv2020

SWR1-independent association of H2A.Z to the LINC complex promotes meiotic chromosome motion

ABSTRACTThe H2A.Z histone variant is deposited into chromatin by the SWR1 complex affecting multiple aspects of meiosis. Here we describe a SWR1-independent localization of H2A.Z at meiotic telomeres and the centrosome. We demonstrate that H2A.Z colocalizes and interacts with Mps3, the SUN component of the LINC complex that spans the nuclear envelope and links meiotic telomeres to the cytoskeleton promoting meiotic chromosome movement. H2A.Z also interacts with the meiosis-specific Ndj1 protein that anchors telomeres to the nuclear periphery via Mps3. Telomeric localization of H2A.Z depends on Ndj1 and the N-terminal domain of Mps3. Although telomeric attachment to the nuclear envelope is maintained in the absence of H2A.Z, the distribution of Mps3 is altered. The velocity of chromosome movement during meiotic prophase I is reduced in the htz1Δ mutant lacking H2A.Z, but it is unaffected in swr1Δ cells. We reveal that H2A.Z is an additional LINC-associated factor that contributes to promote telomere-driven chromosome motion critical for error-free gametogenesis.Competing Interest StatementThe authors have declared no competing interest.Non-standard abbreviationsBiFCBimolecular Fluorescence ComplementationDICDifferential Interference ContrastKAcPotassium AcetateNENuclear EnvelopeLINCLinker of the Nucleoskeleton and CytoskeletonrDNARibosomal DNASCSynaptonemal ComplexSIMStructured Illumination MicroscopySPBSpindle Pole BodyVCC-terminal moiety of the Venus fluorescent proteinVNN-terminal moiety of the Venus fluorescent proteinWCEWhole cell extractsView Full Text

cell biology↗

bioRxiv2019

Topoisomerases modulate the timing of meiotic DNA breakage and repair

During meiotic prophase, concurrent transcription, recombination, and chromosome synapsis, place substantial topological strain on chromosomal DNA, but the role of topoisomerases in this context remains poorly defined. Here, we analyzed the roles topoisomerases I and II (Top1 and Top2) during meiotic prophase in Saccharomyces cerevisiae. We show that both topoisomerases accumulate primarily in promoter-containing intergenic regions of actively transcribing genes. Enrichment partially overlaps meiotic double-strand break (DSB) hotspots, but disruption of either topoisomerase has different effects during meiotic recombination. TOP1 disruption delays DSB induction and shortens the window of DSB accumulation by an unknown mechanism. By contrast, temperature-sensitive top2-1 mutants accumulate DSBs on synapsed chromosomes and exhibit a marked delay in meiotic chromosome remodeling. This defect results from a delay in recruiting the meiotic chromosome remodeler Pch2/TRIP13 but, unexpectedly, is not due to a loss of Top2 catalytic activity. Instead, mutant Top2-1 protein has reduced contact with chromatin but remains associated with meiotic chromosomes, and we provide evidence that this altered binding is responsible for the delay in chromosome remodeling. Our results imply independent roles for topoisomerases I and II in modulating meiotic recombination.

genomics↗