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  1. Article: The Chromatin Landscape Channels DNA Double-Strand Breaks to Distinct Repair Pathways.

    Chen, Zulong / Tyler, Jessica K

    Frontiers in cell and developmental biology

    2022  Volume 10, Page(s) 909696

    Abstract: DNA double-strand breaks (DSBs), the most deleterious DNA lesions, are primarily repaired by two pathways, namely homologous recombination (HR) and non-homologous end joining (NHEJ), the choice of which is largely dependent on cell cycle phase and the ... ...

    Abstract DNA double-strand breaks (DSBs), the most deleterious DNA lesions, are primarily repaired by two pathways, namely homologous recombination (HR) and non-homologous end joining (NHEJ), the choice of which is largely dependent on cell cycle phase and the local chromatin landscape. Recent studies have revealed that post-translational modifications on histones play pivotal roles in regulating DSB repair pathways including repair pathway choice. In this review, we present our current understanding of how these DSB repair pathways are employed in various chromatin landscapes to safeguard genomic integrity. We place an emphasis on the impact of different histone post-translational modifications, characteristic of euchromatin or heterochromatin regions, on DSB repair pathway choice. We discuss the potential roles of damage-induced chromatin modifications in the maintenance of genome and epigenome integrity. Finally, we discuss how RNA transcripts from the vicinity of DSBs at actively transcribed regions also regulate DSB repair pathway choice.
    Language English
    Publishing date 2022-06-08
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2022.909696
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The Chromatin Landscape Channels DNA Double-Strand Breaks to Distinct Repair Pathways

    Zulong Chen / Jessica K. Tyler

    Frontiers in Cell and Developmental Biology, Vol

    2022  Volume 10

    Abstract: DNA double-strand breaks (DSBs), the most deleterious DNA lesions, are primarily repaired by two pathways, namely homologous recombination (HR) and non-homologous end joining (NHEJ), the choice of which is largely dependent on cell cycle phase and the ... ...

    Abstract DNA double-strand breaks (DSBs), the most deleterious DNA lesions, are primarily repaired by two pathways, namely homologous recombination (HR) and non-homologous end joining (NHEJ), the choice of which is largely dependent on cell cycle phase and the local chromatin landscape. Recent studies have revealed that post-translational modifications on histones play pivotal roles in regulating DSB repair pathways including repair pathway choice. In this review, we present our current understanding of how these DSB repair pathways are employed in various chromatin landscapes to safeguard genomic integrity. We place an emphasis on the impact of different histone post-translational modifications, characteristic of euchromatin or heterochromatin regions, on DSB repair pathway choice. We discuss the potential roles of damage-induced chromatin modifications in the maintenance of genome and epigenome integrity. Finally, we discuss how RNA transcripts from the vicinity of DSBs at actively transcribed regions also regulate DSB repair pathway choice.
    Keywords repair pathway choice ; euchromatin ; heterochromatin ; histone modifications ; transcription ; RNA-DNA hybrids ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2022-06-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: A new era for research into aging.

    Kaeberlein, Matt / Tyler, Jessica K

    eLife

    2021  Volume 10

    Abstract: eLife is publishing a special issue on aging, geroscience and longevity to mark the rapid progress made in this field over the past decade, both in terms of mechanistic understanding and translational approaches that are poised to have clinical impact on ...

    Abstract eLife is publishing a special issue on aging, geroscience and longevity to mark the rapid progress made in this field over the past decade, both in terms of mechanistic understanding and translational approaches that are poised to have clinical impact on age-related diseases.
    MeSH term(s) Aging ; Geroscience ; Humans ; Longevity
    Language English
    Publishing date 2021-01-28
    Publishing country England
    Document type Editorial ; Research Support, N.I.H., Extramural
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.65286
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  4. Article ; Online: A new era for research into aging

    Matt Kaeberlein / Jessica K Tyler

    eLife, Vol

    2021  Volume 10

    Abstract: eLife is publishing a special issue on aging, geroscience and longevity to mark the rapid progress made in this field over the past decade, both in terms of mechanistic understanding and translational approaches that are poised to have clinical impact on ...

    Abstract eLife is publishing a special issue on aging, geroscience and longevity to mark the rapid progress made in this field over the past decade, both in terms of mechanistic understanding and translational approaches that are poised to have clinical impact on age-related diseases.
    Keywords aging ; geroscience ; longevity ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: A Proximity Ligation Method to Detect Proteins Bound to Single-Stranded DNA after DNA End Resection at DNA Double-Strand Breaks.

    Fowler, Faith C / Tyler, Jessica K

    Methods and protocols

    2021  Volume 5, Issue 1

    Abstract: After a DNA double-strand break, cells utilize either non-homologous end joining or homologous recombination to repair the broken DNA ends. Homologous recombination requires extensive nucleolytic processing of one of the DNA strands, resulting in long ... ...

    Abstract After a DNA double-strand break, cells utilize either non-homologous end joining or homologous recombination to repair the broken DNA ends. Homologous recombination requires extensive nucleolytic processing of one of the DNA strands, resulting in long stretches of 3' single-strand DNA overhangs. Typically, single-stranded DNA is measured using immunofluorescence microscopy to image the foci of replication protein A, a single-stranded DNA-binding protein. Microscopy analysis of bromodeoxyuridine foci under nondenaturing conditions has also been used to measure single-stranded DNA. Here, we describe a proximity ligation assay which uses genome-wide bromodeoxyuridine incorporation to label single-stranded DNA in order to measure the association of a protein of interest with single-stranded DNA. This method is advantageous over traditional foci analysis because it is more direct and specific than traditional foci co-localization microscopy methods, uses only one color channel, and can reveal protein-single-stranded DNA interactions that are rare and potentially undetectable using traditional microscopy methods. We show here the association of replication protein A and bromodeoxyuridine as proof-of-concept.
    Language English
    Publishing date 2021-12-29
    Publishing country Switzerland
    Document type Journal Article
    ISSN 2409-9279
    ISSN (online) 2409-9279
    DOI 10.3390/mps5010003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: A Flow Cytometry-Based Method for Analyzing DNA End Resection in G

    Chen, Bo-Ruei / Tyler, Jessica K / Sleckman, Barry P

    Bio-protocol

    2022  Volume 12, Issue 10, Page(s) e4413

    Abstract: DNA double strand breaks (DSBs) constantly arise in cells during normal cellular processes or upon exposure to genotoxic agents, and are repaired mostly by homologous recombination (HR) and non-homologous end joining (NHEJ). One key determinant of DNA ... ...

    Abstract DNA double strand breaks (DSBs) constantly arise in cells during normal cellular processes or upon exposure to genotoxic agents, and are repaired mostly by homologous recombination (HR) and non-homologous end joining (NHEJ). One key determinant of DNA DSB repair pathway choice is the processing of broken DNA ends to generate single strand DNA (ssDNA) overhangs, a process termed DNA resection. The generation of ssDNA overhangs commits DSB repair through HR and inhibits NHEJ. Therefore, DNA resection must be carefully regulated to avoid mis-repaired or persistent DSBs. Accordingly, many approaches have been developed to monitor ssDNA generation in cells to investigate genes and pathways that regulate DNA resection. Here we describe a flow cytometric approach measuring the levels of replication protein A (RPA) complex, a high affinity ssDNA binding complex composed of three subunits (RPA70, RPA32, and RPA14 in mammals), on chromatin after DNA DSB induction to assay DNA resection. This flow cytometric assay requires only conventional flow cytometers and can easily be scaled up to analyze a large number of samples or even for genetic screens of pooled mutants on a genome-wide scale. We adopt this assay in G
    Language English
    Publishing date 2022-05-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2833269-6
    ISSN 2331-8325 ; 2331-8325
    ISSN (online) 2331-8325
    ISSN 2331-8325
    DOI 10.21769/BioProtoc.4413
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: A Simple, Improved Method for Scarless Genome Editing of Budding Yeast Using CRISPR-Cas9.

    Aguilar, Rhiannon R / Shen, Zih-Jie / Tyler, Jessica K

    Methods and protocols

    2022  Volume 5, Issue 5

    Abstract: Until recently, the favored method for making directed modifications to the budding yeast genome involved the introduction of a DNA template carrying the desired genetic changes along with a selectable marker, flanked by homology arms. This approach both ...

    Abstract Until recently, the favored method for making directed modifications to the budding yeast genome involved the introduction of a DNA template carrying the desired genetic changes along with a selectable marker, flanked by homology arms. This approach both limited the ability to make changes within genes due to disruption by the introduced selectable marker and prevented the use of that selectable marker for subsequent genomic manipulations. Following the discovery of CRISPR-Cas9-mediated genome editing, protocols were developed for modifying any DNA region of interest in a similar single transformation step without the need for a permanent selectable marker. This approach involves the generation of a DNA double-strand break (DSB) at the desired genomic location by the Cas9 nuclease, expressed on a plasmid which also expresses the guide RNA (gRNA) sequence directing the location of the DSB. The DSB is subsequently repaired via homologous recombination using a PCR-derived DNA repair template. Here, we describe in detail an improved method for incorporation of the gRNA-encoding DNA sequences into the Cas9 expression plasmid. Using Golden Gate cloning, annealed oligonucleotides bearing unique single-strand DNA overhangs are ligated into directional restriction enzyme sites. We describe the use of this CRISPR-Cas9 genome editing protocol to introduce multiple types of directed genetic changes into the yeast genome.
    Language English
    Publishing date 2022-10-04
    Publishing country Switzerland
    Document type Journal Article
    ISSN 2409-9279
    ISSN (online) 2409-9279
    DOI 10.3390/mps5050079
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Nucleosomes Find Their Place in Life.

    Tyler, Jessica K

    Trends in genetics : TIG

    2016  Volume 32, Issue 11, Page(s) 689–690

    Abstract: To carry epigenetic information, the chromatin structure must be accurately rebuilt after its deconstruction during genomic replication. Using an elegant, novel approach, Vasseur et al.[1] reveal that transcription plays a key role in sculpting the ... ...

    Abstract To carry epigenetic information, the chromatin structure must be accurately rebuilt after its deconstruction during genomic replication. Using an elegant, novel approach, Vasseur et al.[1] reveal that transcription plays a key role in sculpting the chromatin after DNA replication.
    MeSH term(s) Chromatin/genetics ; DNA Replication/genetics ; Epigenesis, Genetic/genetics ; Genome/genetics ; Histones/genetics ; Humans ; Nucleosomes/genetics ; Transcription, Genetic
    Chemical Substances Chromatin ; Histones ; Nucleosomes
    Language English
    Publishing date 2016-11
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 619240-3
    ISSN 1362-4555 ; 0168-9525 ; 0168-9479
    ISSN (online) 1362-4555
    ISSN 0168-9525 ; 0168-9479
    DOI 10.1016/j.tig.2016.09.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  9. Article ; Online: A Proximity Ligation Method to Detect Proteins Bound to Single-Stranded DNA after DNA End Resection at DNA Double-Strand Breaks

    Faith C. Fowler / Jessica K. Tyler

    Methods and Protocols, Vol 5, Iss 3, p

    2022  Volume 3

    Abstract: After a DNA double-strand break, cells utilize either non-homologous end joining or homologous recombination to repair the broken DNA ends. Homologous recombination requires extensive nucleolytic processing of one of the DNA strands, resulting in long ... ...

    Abstract After a DNA double-strand break, cells utilize either non-homologous end joining or homologous recombination to repair the broken DNA ends. Homologous recombination requires extensive nucleolytic processing of one of the DNA strands, resulting in long stretches of 3′ single-strand DNA overhangs. Typically, single-stranded DNA is measured using immunofluorescence microscopy to image the foci of replication protein A, a single-stranded DNA-binding protein. Microscopy analysis of bromodeoxyuridine foci under nondenaturing conditions has also been used to measure single-stranded DNA. Here, we describe a proximity ligation assay which uses genome-wide bromodeoxyuridine incorporation to label single-stranded DNA in order to measure the association of a protein of interest with single-stranded DNA. This method is advantageous over traditional foci analysis because it is more direct and specific than traditional foci co-localization microscopy methods, uses only one color channel, and can reveal protein-single-stranded DNA interactions that are rare and potentially undetectable using traditional microscopy methods. We show here the association of replication protein A and bromodeoxyuridine as proof-of-concept.
    Keywords single-stranded DNA ; proximity ligation assay ; DNA end resection ; double-strand break repair ; Biology (General) ; QH301-705.5
    Subject code 612
    Language English
    Publishing date 2022-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article: Chronic constipation and abdominal distension in a patient with adult Hirschprung's disease and bilateral ovarian teratomas.

    Vo, Jessica / Hayler, Raymond / Tyler, Alex / Verschuer, Kurt

    Journal of surgical case reports

    2024  Volume 2024, Issue 4, Page(s) rjae227

    Abstract: Hirschprung's disease is a congenital disorder characterized by aganglionic bowel, usually diagnosed in infancy. Here, we present a unique case of Hirschprung's disease diagnosed in a 29-year-old female with acute on chronic constipation. As part of her ... ...

    Abstract Hirschprung's disease is a congenital disorder characterized by aganglionic bowel, usually diagnosed in infancy. Here, we present a unique case of Hirschprung's disease diagnosed in a 29-year-old female with acute on chronic constipation. As part of her work up, a computerized tomography of her abdomen and pelvis revealed large, bilateral dermoid cysts. A diagnostic and therapeutic colonoscopy allowed manual disimpaction and decompression of her bowel, as well as biopsy attainment. Histopathology revealed absence of ganglionic cells on haematoxylin and eosin stain and calretinin immunostaining. This case underscores the diagnostic challenges of Adult Hirschprung's disease and how this impacts patient quality of life, as well as the work up and management of concurrent causes abdominopelvic conditions.
    Language English
    Publishing date 2024-04-18
    Publishing country England
    Document type Case Reports
    ZDB-ID 2580919-2
    ISSN 2042-8812
    ISSN 2042-8812
    DOI 10.1093/jscr/rjae227
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