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  1. Article ; Online: G1-Cyclin2 (Cln2) promotes chromosome hypercondensation in eco1/ctf7 rad61 null cells during hyperthermic stress in Saccharomyces cerevisiae.

    Buskirk, Sean / Skibbens, Robert V

    G3 (Bethesda, Md.)

    2022  Volume 12, Issue 8

    Abstract: ... result in severe developmental abnormalities and intellectual disabilities referred to as Roberts ...

    Abstract Eco1/Ctf7 is a highly conserved acetyltransferase that activates cohesin complexes and is critical for sister chromatid cohesion, chromosome condensation, DNA damage repair, nucleolar integrity, and gene transcription. Mutations in the human homolog of ECO1 (ESCO2/EFO2), or in genes that encode cohesin subunits, result in severe developmental abnormalities and intellectual disabilities referred to as Roberts syndrome and Cornelia de Lange syndrome, respectively. In yeast, deletion of ECO1 results in cell inviability. Codeletion of RAD61 (WAPL in humans), however, produces viable yeast cells. These eco1 rad61 double mutants, however, exhibit a severe temperature-sensitive growth defect, suggesting that Eco1 or cohesins respond to hyperthermic stress through a mechanism that occurs independent of Rad61. Here, we report that deletion of the G1 cyclin CLN2 rescues the temperature-sensitive lethality otherwise exhibited by eco1 rad61 mutant cells, such that the triple mutant cells exhibit robust growth over a broad range of temperatures. While Cln1, Cln2, and Cln3 are functionally redundant G1 cyclins, neither CLN1 nor CLN3 deletions rescue the temperature-sensitive growth defects otherwise exhibited by eco1 rad61 double mutants. We further provide evidence that CLN2 deletion rescues hyperthermic growth defects independent of START and impacts the state of chromosome condensation. These findings reveal novel roles for Cln2 that are unique among the G1 cyclin family and appear critical for cohesin regulation during hyperthermic stress.
    MeSH term(s) Acetyltransferases/genetics ; Cell Cycle Proteins/genetics ; Chromatids ; Chromosomal Proteins, Non-Histone/genetics ; Chromosome Segregation ; Cyclins/genetics ; Humans ; Lymphocytes, Null ; Membrane Glycoproteins/genetics ; Molecular Chaperones/genetics ; Nuclear Proteins/genetics ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae Proteins/genetics
    Chemical Substances CLN2 protein, S cerevisiae ; CLN3 protein, human ; Cell Cycle Proteins ; Chromosomal Proteins, Non-Histone ; Cyclins ; Membrane Glycoproteins ; Molecular Chaperones ; Nuclear Proteins ; RAD61 protein, S cerevisiae ; Saccharomyces cerevisiae Proteins ; Acetyltransferases (EC 2.3.1.-) ; ECO1 protein, S cerevisiae (EC 2.3.1.-) ; ESCO2 protein, human (EC 2.3.1.-)
    Language English
    Publishing date 2022-06-22
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2629978-1
    ISSN 2160-1836 ; 2160-1836
    ISSN (online) 2160-1836
    ISSN 2160-1836
    DOI 10.1093/g3journal/jkac157
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Integrating Sister Chromatid Cohesion Establishment to DNA Replication.

    Zuilkoski, Caitlin M / Skibbens, Robert V

    Genes

    2022  Volume 13, Issue 4

    Abstract: The intersection through which two fundamental processes meet provides a unique vantage point from which to view cellular regulation. On the one hand, DNA replication is at the heart of cell division, generating duplicate chromosomes that allow each ... ...

    Abstract The intersection through which two fundamental processes meet provides a unique vantage point from which to view cellular regulation. On the one hand, DNA replication is at the heart of cell division, generating duplicate chromosomes that allow each daughter cell to inherit a complete copy of the parental genome. Among other factors, the PCNA (proliferating cell nuclear antigen) sliding clamp ensures processive DNA replication during S phase and is essential for cell viability. On the other hand, the process of chromosome segregation during M phase-an act that occurs long after DNA replication-is equally fundamental to a successful cell division. Eco1/Ctf7 ensures that chromosomes faithfully segregate during mitosis, but functions during DNA replication to activate cohesins and thereby establish cohesion between sister chromatids. To achieve this, Eco1 binds PCNA and numerous other DNA replication fork factors that include MCM helicase, Chl1 helicase, and the Rtt101-Mms1-Mms22 E3 ubiquitin ligase. Here, we review the multi-faceted coordination between cohesion establishment and DNA replication. SUMMARY STATEMENT: New findings provide important insights into the mechanisms through which DNA replication and the establishment of sister chromatid cohesion are coupled.
    MeSH term(s) Acetyltransferases/genetics ; Chromatids/genetics ; Chromosome Segregation ; DNA Replication/genetics ; Nuclear Proteins/genetics ; Proliferating Cell Nuclear Antigen/genetics ; Proliferating Cell Nuclear Antigen/metabolism ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae Proteins/genetics
    Chemical Substances Nuclear Proteins ; Proliferating Cell Nuclear Antigen ; Saccharomyces cerevisiae Proteins ; Acetyltransferases (EC 2.3.1.-) ; ECO1 protein, S cerevisiae (EC 2.3.1.-)
    Language English
    Publishing date 2022-03-31
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 2527218-4
    ISSN 2073-4425 ; 2073-4425
    ISSN (online) 2073-4425
    ISSN 2073-4425
    DOI 10.3390/genes13040625
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Condensins and cohesins - one of these things is not like the other!

    Skibbens, Robert V

    Journal of cell science

    2019  Volume 132, Issue 3

    Abstract: Condensins and cohesins are highly conserved complexes that tether together DNA loci within a single DNA molecule to produce DNA loops. Condensin and cohesin structures, however, are different, and the DNA loops produced by each underlie distinct cell ... ...

    Abstract Condensins and cohesins are highly conserved complexes that tether together DNA loci within a single DNA molecule to produce DNA loops. Condensin and cohesin structures, however, are different, and the DNA loops produced by each underlie distinct cell processes. Condensin rods compact chromosomes during mitosis, with condensin I and II complexes producing spatially defined and nested looping in metazoan cells. Structurally adaptive cohesin rings produce loops, which organize the genome during interphase. Cohesin-mediated loops, termed topologically associating domains or TADs, antagonize the formation of epigenetically defined but untethered DNA volumes, termed compartments. While condensin complexes formed through
    MeSH term(s) Adenosine Triphosphatases/genetics ; Adenosine Triphosphatases/metabolism ; Adenosine Triphosphatases/ultrastructure ; Animals ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; Cell Cycle Proteins/ultrastructure ; Chromatin/metabolism ; Chromatin/ultrastructure ; Chromosomal Proteins, Non-Histone/genetics ; Chromosomal Proteins, Non-Histone/metabolism ; Chromosomal Proteins, Non-Histone/ultrastructure ; DNA/genetics ; DNA/metabolism ; DNA/ultrastructure ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; DNA-Binding Proteins/ultrastructure ; Genome ; Interphase ; Mitosis ; Multiprotein Complexes/genetics ; Multiprotein Complexes/metabolism ; Multiprotein Complexes/ultrastructure ; Protein Binding ; Protein Isoforms/genetics ; Protein Isoforms/metabolism ; Protein Isoforms/ultrastructure ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae/ultrastructure ; Cohesins
    Chemical Substances Cell Cycle Proteins ; Chromatin ; Chromosomal Proteins, Non-Histone ; DNA-Binding Proteins ; Multiprotein Complexes ; Protein Isoforms ; condensin complexes ; DNA (9007-49-2) ; Adenosine Triphosphatases (EC 3.6.1.-)
    Language English
    Publishing date 2019-02-07
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2993-2
    ISSN 1477-9137 ; 0021-9533
    ISSN (online) 1477-9137
    ISSN 0021-9533
    DOI 10.1242/jcs.220491
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Genetically induced redox stress occurs in a yeast model for Roberts syndrome.

    Mfarej, Michael G / Skibbens, Robert V

    G3 (Bethesda, Md.)

    2021  Volume 12, Issue 2

    Abstract: Roberts syndrome (RBS) is a multispectrum developmental disorder characterized by severe limb ...

    Abstract Roberts syndrome (RBS) is a multispectrum developmental disorder characterized by severe limb, craniofacial, and organ abnormalities and often intellectual disabilities. The genetic basis of RBS is rooted in loss-of-function mutations in the essential N-acetyltransferase ESCO2 which is conserved from yeast (Eco1/Ctf7) to humans. ESCO2/Eco1 regulate many cellular processes that impact chromatin structure, chromosome transmission, gene expression, and repair of the genome. The etiology of RBS remains contentious with current models that include transcriptional dysregulation or mitotic failure. Here, we report evidence that supports an emerging model rooted in defective DNA damage responses. First, the results reveal that redox stress is elevated in both eco1 and cohesion factor Saccharomyces cerevisiae mutant cells. Second, we provide evidence that Eco1 and cohesion factors are required for the repair of oxidative DNA damage such that ECO1 and cohesin gene mutations result in reduced cell viability and hyperactivation of DNA damage checkpoints that occur in response to oxidative stress. Moreover, we show that mutation of ECO1 is solely sufficient to induce endogenous redox stress and sensitizes mutant cells to exogenous genotoxic challenges. Remarkably, antioxidant treatment desensitizes eco1 mutant cells to a range of DNA damaging agents, raising the possibility that modulating the cellular redox state may represent an important avenue of treatment for RBS and tumors that bear ESCO2 mutations.
    MeSH term(s) Acetyltransferases/genetics ; Acetyltransferases/metabolism ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; Chromatids ; Chromosomal Proteins, Non-Histone/genetics ; Chromosomal Proteins, Non-Histone/metabolism ; Craniofacial Abnormalities ; Ectromelia/genetics ; Ectromelia/metabolism ; Ectromelia/pathology ; Humans ; Hypertelorism/genetics ; Hypertelorism/metabolism ; Hypertelorism/pathology ; Nuclear Proteins/genetics ; Oxidation-Reduction ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism
    Chemical Substances Cell Cycle Proteins ; Chromosomal Proteins, Non-Histone ; Nuclear Proteins ; Saccharomyces cerevisiae Proteins ; Acetyltransferases (EC 2.3.1.-) ; ECO1 protein, S cerevisiae (EC 2.3.1.-) ; ESCO2 protein, human (EC 2.3.1.-)
    Language English
    Publishing date 2021-12-12
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2629978-1
    ISSN 2160-1836 ; 2160-1836
    ISSN (online) 2160-1836
    ISSN 2160-1836
    DOI 10.1093/g3journal/jkab426
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Correction: Chl1 DNA helicase and Scc2 function in chromosome condensation through cohesin deposition.

    Shen, Donglai / Skibbens, Robert V

    PloS one

    2020  Volume 15, Issue 1, Page(s) e0227443

    Abstract: This corrects the article DOI: 10.1371/journal.pone.0188739.]. ...

    Abstract [This corrects the article DOI: 10.1371/journal.pone.0188739.].
    Language English
    Publishing date 2020-01-10
    Publishing country United States
    Document type Published Erratum
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0227443
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: An ever-changing landscape in Roberts syndrome biology: Implications for macromolecular damage.

    Mfarej, Michael G / Skibbens, Robert V

    PLoS genetics

    2020  Volume 16, Issue 12, Page(s) e1009219

    Abstract: Roberts syndrome (RBS) is a rare developmental disorder that can include craniofacial abnormalities ...

    Abstract Roberts syndrome (RBS) is a rare developmental disorder that can include craniofacial abnormalities, limb malformations, missing digits, intellectual disabilities, stillbirth, and early mortality. The genetic basis for RBS is linked to autosomal recessive loss-of-function mutation of the establishment of cohesion (ESCO) 2 acetyltransferase. ESCO2 is an essential gene that targets the DNA-binding cohesin complex. ESCO2 acetylates alternate subunits of cohesin to orchestrate vital cellular processes that include sister chromatid cohesion, chromosome condensation, transcription, and DNA repair. Although significant advances were made over the last 20 years in our understanding of ESCO2 and cohesin biology, the molecular etiology of RBS remains ambiguous. In this review, we highlight current models of RBS and reflect on data that suggests a novel role for macromolecular damage in the molecular etiology of RBS.
    MeSH term(s) Acetyltransferases/genetics ; Acetyltransferases/metabolism ; Animals ; Chromosomal Proteins, Non-Histone/genetics ; Chromosomal Proteins, Non-Histone/metabolism ; Craniofacial Abnormalities/genetics ; Craniofacial Abnormalities/metabolism ; DNA Damage ; Ectromelia/genetics ; Ectromelia/metabolism ; Genomic Instability ; Humans ; Hypertelorism/genetics ; Hypertelorism/metabolism
    Chemical Substances Chromosomal Proteins, Non-Histone ; Acetyltransferases (EC 2.3.1.-) ; ESCO2 protein, human (EC 2.3.1.-)
    Language English
    Publishing date 2020-12-31
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2186725-2
    ISSN 1553-7404 ; 1553-7390
    ISSN (online) 1553-7404
    ISSN 1553-7390
    DOI 10.1371/journal.pgen.1009219
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  7. Article ; Online: PCNA promotes context-specific sister chromatid cohesion establishment separate from that of chromatin condensation.

    Zuilkoski, Caitlin M / Skibbens, Robert V

    Cell cycle (Georgetown, Tex.)

    2020  Volume 19, Issue 19, Page(s) 2436–2450

    Abstract: Cellular genomes undergo various structural changes that ... ...

    Abstract Cellular genomes undergo various structural changes that include
    MeSH term(s) Acetylation ; Acetyltransferases/genetics ; Acetyltransferases/metabolism ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; Chromatids ; Chromatin Assembly and Disassembly ; Chromosomal Proteins, Non-Histone/genetics ; Chromosomal Proteins, Non-Histone/metabolism ; Chromosomes, Fungal ; DNA Replication ; DNA, Fungal/biosynthesis ; DNA, Fungal/genetics ; Mutation ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; Proliferating Cell Nuclear Antigen/genetics ; Proliferating Cell Nuclear Antigen/metabolism ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism ; Cohesins
    Chemical Substances Carrier Proteins ; Cell Cycle Proteins ; Chromosomal Proteins, Non-Histone ; DNA, Fungal ; Elg1 protein, S cerevisiae ; Nuclear Proteins ; POL30 protein, S cerevisiae ; Proliferating Cell Nuclear Antigen ; SMC3 protein, S cerevisiae ; Saccharomyces cerevisiae Proteins ; Acetyltransferases (EC 2.3.1.-) ; ECO1 protein, S cerevisiae (EC 2.3.1.-)
    Language English
    Publishing date 2020-09-14
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2146183-1
    ISSN 1551-4005 ; 1538-4101 ; 1554-8627
    ISSN (online) 1551-4005
    ISSN 1538-4101 ; 1554-8627
    DOI 10.1080/15384101.2020.1804221
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Promotion of Hyperthermic-Induced rDNA Hypercondensation in

    Shen, Donglai / Skibbens, Robert V

    Genetics

    2020  Volume 214, Issue 3, Page(s) 589–604

    Abstract: Ribosome biogenesis is tightly regulated through stress-sensing pathways that impact genome stability, aging and senescence. ... ...

    Abstract Ribosome biogenesis is tightly regulated through stress-sensing pathways that impact genome stability, aging and senescence. In
    MeSH term(s) Adenosine Triphosphatases/genetics ; Adenosine Triphosphatases/ultrastructure ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/ultrastructure ; Chromosomal Proteins, Non-Histone/genetics ; Chromosomal Proteins, Non-Histone/ultrastructure ; Chromosomes, Fungal/genetics ; DNA, Ribosomal/genetics ; DNA, Ribosomal/ultrastructure ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/ultrastructure ; HSP90 Heat-Shock Proteins/genetics ; High Mobility Group Proteins/genetics ; High Mobility Group Proteins/ultrastructure ; Mitosis/genetics ; Multiprotein Complexes/genetics ; Multiprotein Complexes/ultrastructure ; Nucleic Acid Conformation ; Ribosomes/genetics ; Ribosomes/ultrastructure ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/ultrastructure ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/ultrastructure ; Cohesins
    Chemical Substances Cell Cycle Proteins ; Chromosomal Proteins, Non-Histone ; DNA, Ribosomal ; DNA-Binding Proteins ; HMO1 protein, S cerevisiae ; HSP82 protein, S cerevisiae ; HSP90 Heat-Shock Proteins ; High Mobility Group Proteins ; Multiprotein Complexes ; Saccharomyces cerevisiae Proteins ; condensin complexes ; Adenosine Triphosphatases (EC 3.6.1.-)
    Language English
    Publishing date 2020-01-24
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2167-2
    ISSN 1943-2631 ; 0016-6731
    ISSN (online) 1943-2631
    ISSN 0016-6731
    DOI 10.1534/genetics.119.302994
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  9. Article ; Online: Correction: Of Rings and Rods: Regulating Cohesin Entrapment of DNA to Generate Intra- and Intermolecular Tethers.

    Skibbens, Robert V

    PLoS genetics

    2016  Volume 12, Issue 12, Page(s) e1006478

    Abstract: This corrects the article DOI: 10.1371/journal.pgen.1006337.]. ...

    Abstract [This corrects the article DOI: 10.1371/journal.pgen.1006337.].
    Language English
    Publishing date 2016-12-01
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 2186725-2
    ISSN 1553-7404 ; 1553-7390
    ISSN (online) 1553-7404
    ISSN 1553-7390
    DOI 10.1371/journal.pgen.1006478
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  10. Article ; Online: DNA damage induces Yap5-dependent transcription of ECO1/CTF7 in Saccharomyces cerevisiae.

    Mfarej, Michael G / Skibbens, Robert V

    PloS one

    2020  Volume 15, Issue 12, Page(s) e0242968

    Abstract: Yeast Eco1 (ESCO2 in humans) acetyltransferase converts chromatin-bound cohesins to a DNA tethering state, thereby establishing sister chromatid cohesion. Eco1 establishes cohesion during DNA replication, after which Eco1 is targeted for degradation by ... ...

    Abstract Yeast Eco1 (ESCO2 in humans) acetyltransferase converts chromatin-bound cohesins to a DNA tethering state, thereby establishing sister chromatid cohesion. Eco1 establishes cohesion during DNA replication, after which Eco1 is targeted for degradation by SCF E3 ubiquitin ligase. SCF E3 ligase, and sequential phosphorylations that promote Eco1 ubiquitination and degradation, remain active throughout the M phase. In this way, Eco1 protein levels are high during S phase, but remain low throughout the remaining cell cycle. In response to DNA damage during M phase, however, Eco1 activity increases-providing for a new wave of cohesion establishment (termed Damage-Induced Cohesion, or DIC) which is critical for efficient DNA repair. To date, little evidence exists as to the mechanism through which Eco1 activity increases during M phase in response to DNA damage. Possibilities include that either the kinases or E3 ligase, that target Eco1 for degradation, are inhibited in response to DNA damage. Our results reveal instead that the degradation machinery remains fully active during M phase, despite the presence of DNA damage. In testing alternate models through which Eco1 activity increases in response to DNA damage, the results reveal that DNA damage induces new transcription of ECO1 and at a rate that exceeds the rate of Eco1 turnover, providing for rapid accumulation of Eco1 protein. We further show that DNA damage induction of ECO1 transcription is in part regulated by Yap5-a stress-induced transcription factor. Given the role for mutated ESCO2 (homolog of ECO1) in human birth defects, this study highlights the complex nature through which mutation of ESCO2, and defects in ESCO2 regulation, may promote developmental abnormalities and contribute to various diseases including cancer.
    MeSH term(s) Acetyltransferases/genetics ; Basic-Leucine Zipper Transcription Factors/metabolism ; DNA Damage ; Nuclear Proteins/genetics ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism ; Transcription, Genetic
    Chemical Substances Basic-Leucine Zipper Transcription Factors ; Nuclear Proteins ; Saccharomyces cerevisiae Proteins ; Yap5 protein, S cerevisiae ; Acetyltransferases (EC 2.3.1.-) ; ECO1 protein, S cerevisiae (EC 2.3.1.-)
    Language English
    Publishing date 2020-12-29
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0242968
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