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  • 1
    Online Resource
    Online Resource
    Dna2 removes toxic ssDNA-RPA filaments generated from meiotic recombination-associated DNA synthesis
    Oxford University Press (OUP) ; 2023
    In:  Nucleic Acids Research Vol. 51, No. 15 ( 2023-08-25), p. 7914-7935
    Details
    In: Nucleic Acids Research, Oxford University Press (OUP), Vol. 51, No. 15 ( 2023-08-25), p. 7914-7935
    Abstract: During the repair of DNA double-strand breaks (DSBs), de novo synthesized DNA strands can displace the parental strand to generate single-strand DNAs (ssDNAs). Many programmed DSBs and thus many ssDNAs occur during meiosis. However, it is unclear how these ssDNAs are removed for the complete repair of meiotic DSBs. Here, we show that meiosis-specific depletion of Dna2 (dna2-md) results in an abundant accumulation of RPA and an expansion of RPA from DSBs to broader regions in Saccharomyces cerevisiae. As a result, DSB repair is defective and spores are inviable, although the levels of crossovers/non-crossovers seem to be unaffected. Furthermore, Dna2 induction at pachytene is highly effective in removing accumulated RPA and restoring spore viability. Moreover, the depletion of Pif1, an activator of polymerase δ required for meiotic recombination-associated DNA synthesis, and Pif1 inhibitor Mlh2 decreases and increases RPA accumulation in dna2-md, respectively. In addition, blocking DNA synthesis during meiotic recombination dramatically decreases RPA accumulation in dna2-md. Together, our findings show that meiotic DSB repair requires Dna2 to remove ssDNA-RPA filaments generated from meiotic recombination-associated DNA synthesis. Additionally, we showed that Dna2 also regulates DSB-independent RPA distribution.
    Type of Medium: Online Resource
    ISSN: 0305-1048 , 1362-4962
    URL: Article
    DOI: 10.1093/nar/gkad537
    RVK:
    WA 15000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1472175-2
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Interplay between Pds5 and Rec8 in regulating chromosome axis length and crossover frequency
    American Association for the Advancement of Science (AAAS) ; 2021
    In:  Science Advances Vol. 7, No. 11 ( 2021-03-12)
    Details
    In: Science Advances, American Association for the Advancement of Science (AAAS), Vol. 7, No. 11 ( 2021-03-12)
    Abstract: Meiotic chromosomes have a loop/axis architecture, with axis length determining crossover frequency. Meiosis-specific Pds5 depletion mutants have shorter chromosome axes and lower homologous chromosome pairing and recombination frequency. However, it is poorly understood how Pds5 coordinately regulates these processes. In this study, we show that only ~20% of wild-type level of Pds5 is required for homolog pairing and that higher levels of Pds5 dosage-dependently regulate axis length and crossover frequency. Moderate changes in Pds5 protein levels do not explicitly impair the basic recombination process. Further investigations show that Pds5 does not regulate chromosome axes by altering Rec8 abundance. Conversely, Rec8 regulates chromosome axis length by modulating Pds5. These findings highlight the important role of Pds5 in regulating meiosis and its relationship with Rec8 to regulate chromosome axis length and crossover frequency with implications for evolutionary adaptation.
    Type of Medium: Online Resource
    ISSN: 2375-2548
    URL: Article
    DOI: 10.1126/sciadv.abe7920
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2021
    detail.hit.zdb_id: 2810933-8
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  • 3
    Online Resource
    Online Resource
    Meiotic chromosome organization and crossover patterns
    Oxford University Press (OUP) ; 2022
    In:  Biology of Reproduction Vol. 107, No. 1 ( 2022-07-25), p. 275-288
    Details
    In: Biology of Reproduction, Oxford University Press (OUP), Vol. 107, No. 1 ( 2022-07-25), p. 275-288
    Abstract: Meiosis is the foundation of sexual reproduction, and crossover recombination is one hallmark of meiosis. Crossovers establish the physical connections between homolog chromosomes (homologs) for their proper segregation and exchange DNA between homologs to promote genetic diversity in gametes and thus progenies. Aberrant crossover patterns, e.g., absence of the obligatory crossover, are the leading cause of infertility, miscarriage, and congenital disease. Therefore, crossover patterns have to be tightly controlled. During meiosis, loop/axis organized chromosomes provide the structural basis and regulatory machinery for crossover patterning. Accumulating evidence shows that chromosome axis length regulates the numbers and the positions of crossovers. In addition, recent studies suggest that alterations in axis length and the resultant alterations in crossover frequency may contribute to evolutionary adaptation. Here, current advances regarding these issues are reviewed, the possible mechanisms for axis length regulating crossover frequency are discussed, and important issues that need further investigations are suggested.
    Type of Medium: Online Resource
    ISSN: 0006-3363 , 1529-7268
    URL: Article
    DOI: 10.1093/biolre/ioac040
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1469812-2
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    ESA1 regulates meiotic chromosome axis and crossover frequency via acetylating histone H4
    Oxford University Press (OUP) ; 2021
    In:  Nucleic Acids Research Vol. 49, No. 16 ( 2021-09-20), p. 9353-9373
    Details
    In: Nucleic Acids Research, Oxford University Press (OUP), Vol. 49, No. 16 ( 2021-09-20), p. 9353-9373
    Abstract: Meiotic recombination is integrated into and regulated by meiotic chromosomes, which is organized as loop/axis architecture. However, the regulation of chromosome organization is poorly understood. Here, we show Esa1, the NuA4 complex catalytic subunit, is constitutively expressed and localizes on chromatin loops during meiosis. Esa1 plays multiple roles including homolog synapsis, sporulation efficiency, spore viability, and chromosome segregation in meiosis. Detailed analyses show the meiosis-specific depletion of Esa1 results in decreased chromosome axis length independent of another axis length regulator Pds5, which further leads to a decreased number of Mer2 foci, and consequently a decreased number of DNA double-strand breaks, recombination intermediates, and crossover frequency. However, Esa1 depletion does not impair the occurrence of the obligatory crossover required for faithful chromosome segregation, or the strength of crossover interference. Further investigations demonstrate Esa1 regulates chromosome axis length via acetylating the N-terminal tail of histone H4 but not altering transcription program. Therefore, we firstly show a non-chromosome axis component, Esa1, acetylates histone H4 on chromatin loops to regulate chromosome axis length and consequently recombination frequency but does not affect the basic meiotic recombination process. Additionally, Esa1 depletion downregulates middle induced meiotic genes, which probably causing defects in sporulation and chromosome segregation.
    Type of Medium: Online Resource
    ISSN: 0305-1048 , 1362-4962
    URL: Article
    DOI: 10.1093/nar/gkab722
    RVK:
    WA 15000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1472175-2
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    RNA-DNA hybrids regulate meiotic recombination
    Elsevier BV ; 2021
    In:  Cell Reports Vol. 37, No. 10 ( 2021-12), p. 110097-
    Details
    In: Cell Reports, Elsevier BV, Vol. 37, No. 10 ( 2021-12), p. 110097-
    Type of Medium: Online Resource
    ISSN: 2211-1247
    URL: Article
    DOI: 10.1016/j.celrep.2021.110097
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2649101-1
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  • 6
    Online Resource
    Online Resource
    Negative supercoils regulate meiotic crossover patterns in budding yeast
    Oxford University Press (OUP) ; 2022
    In:  Nucleic Acids Research Vol. 50, No. 18 ( 2022-10-14), p. 10418-10435
    Details
    In: Nucleic Acids Research, Oxford University Press (OUP), Vol. 50, No. 18 ( 2022-10-14), p. 10418-10435
    Abstract: Interference exists ubiquitously in many biological processes. Crossover interference patterns meiotic crossovers, which are required for faithful chromosome segregation and evolutionary adaption. However, what the interference signal is and how it is generated and regulated is unknown. We show that yeast top2 alleles which cannot bind or cleave DNA accumulate a higher level of negative supercoils and show weaker interference. However, top2 alleles which cannot religate the cleaved DNA or release the religated DNA accumulate less negative supercoils and show stronger interference. Moreover, the level of negative supercoils is negatively correlated with crossover interference strength. Furthermore, negative supercoils preferentially enrich at crossover-associated Zip3 regions before the formation of meiotic DNA double-strand breaks, and regions with more negative supercoils tend to have more Zip3. Additionally, the strength of crossover interference and homeostasis change coordinately in mutants. These findings suggest that the accumulation and relief of negative supercoils pattern meiotic crossovers.
    Type of Medium: Online Resource
    ISSN: 0305-1048 , 1362-4962
    URL: Article
    DOI: 10.1093/nar/gkac786
    RVK:
    WA 15000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1472175-2
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    The ubiquitin–proteasome system regulates meiotic chromosome organization
    Proceedings of the National Academy of Sciences ; 2022
    In:  Proceedings of the National Academy of Sciences Vol. 119, No. 17 ( 2022-04-26)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 119, No. 17 ( 2022-04-26)
    Abstract: Meiotic crossover (CO) recombination is tightly regulated by chromosome architecture to ensure faithful chromosome segregation and to reshuffle alleles between parental chromosomes for genetic diversity of progeny. However, regulation of the meiotic chromosome loop/axis organization is poorly understood. Here, we identify a molecular pathway for axis length regulation. We show that the cohesin regulator Pds5 can interact with proteasomes. Meiosis-specific depletion of proteasomes and/or Pds5 results in a similarly shortened chromosome axis, suggesting proteasomes and Pds5 regulate axis length in the same pathway. Protein ubiquitination is accumulated in pds5 and proteasome mutants. Moreover, decreased chromosome axis length in these mutants can be largely rescued by decreasing ubiquitin availability and thus decreasing protein ubiquitination. Further investigation reveals that two ubiquitin E3 ligases, SCF (Skp–Cullin–F-box) and Ufd4, are involved in this Pds5–ubiquitin/proteasome pathway to cooperatively control chromosome axis length. These results support the hypothesis that ubiquitination of chromosome proteins results in a shortened chromosome axis, and cohesin–Pds5 recruits proteasomes onto chromosomes to regulate ubiquitination level and thus axis length. These findings reveal an unexpected role of the ubiquitin–proteasome system in meiosis and contribute to our knowledge of how Pds5 regulates meiotic chromosome organization. A conserved regulatory mechanism probably exists in higher eukaryotes.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2106902119
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2022
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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