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  1. Article ; Online: Is it a wrap? Nucleosome interactions of the BRCA1-binding partner, BARD1, steal the scene.

    Morris, Joanna R

    Nature structural & molecular biology

    2021  Volume 28, Issue 9, Page(s) 708–710

    MeSH term(s) Ankyrin Repeat ; BRCA1 Protein/metabolism ; Cryoelectron Microscopy ; DNA Damage ; Fanconi Anemia Complementation Group N Protein/metabolism ; Histone Code ; Histones/metabolism ; Humans ; Mutation, Missense ; Neoplasm Proteins/metabolism ; Neoplasms/enzymology ; Nucleosomes/metabolism ; Phthalazines/pharmacology ; Piperazines/pharmacology ; Protein Binding ; Protein Domains ; Recombinational DNA Repair ; Tumor Suppressor Proteins/chemistry ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/metabolism ; Ubiquitin-Protein Ligases/chemistry ; Ubiquitin-Protein Ligases/genetics ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitination
    Chemical Substances BRCA1 Protein ; BRCA1 protein, human ; Fanconi Anemia Complementation Group N Protein ; Histones ; Neoplasm Proteins ; Nucleosomes ; PALB2 protein, human ; Phthalazines ; Piperazines ; Tumor Suppressor Proteins ; BARD1 protein, human (EC 2.3.2.27) ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; olaparib (WOH1JD9AR8)
    Language English
    Publishing date 2021-09-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2126708-X
    ISSN 1545-9985 ; 1545-9993
    ISSN (online) 1545-9985
    ISSN 1545-9993
    DOI 10.1038/s41594-021-00658-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: SUMO monoclonal antibodies vary in sensitivity, specificity, and ability to detect types of SUMO conjugate.

    Garvin, Alexander J / Lanz, Alexander J / Morris, Joanna R

    Scientific reports

    2022  Volume 12, Issue 1, Page(s) 21343

    Abstract: Monoclonal antibodies (MAb) to members of the Small Ubiquitin-like modifier (SUMO) family are essential tools in the study of cellular SUMOylation. However, many anti-SUMO MAbs are poorly validated, and antibody matching to detection format is without an ...

    Abstract Monoclonal antibodies (MAb) to members of the Small Ubiquitin-like modifier (SUMO) family are essential tools in the study of cellular SUMOylation. However, many anti-SUMO MAbs are poorly validated, and antibody matching to detection format is without an evidence base. Here we test the specificity and sensitivity of twenty-four anti-SUMO MAbs towards monomeric and polymeric SUMO1-4 in dot-blots, immunoblots, immunofluorescence and immunoprecipitation. We find substantial variability between SUMO MAbs for different conjugation states, for detecting increased SUMOylation in response to thirteen different stress agents, and as enrichment reagents for SUMOylated RanGAP1 or KAP1. All four anti-SUMO4 monoclonal antibodies tested cross-reacted wit SUMO2/3, and several SUMO2/3 monoclonal antibodies cross-reacted with SUMO4. These data characterize the specificity of twenty-four anti-SUMO antibodies across commonly used assays, creating an enabling resource for the SUMO research community.
    MeSH term(s) Small Ubiquitin-Related Modifier Proteins/metabolism ; Antibodies, Monoclonal ; Ubiquitin ; Sumoylation ; Immunoprecipitation
    Chemical Substances Small Ubiquitin-Related Modifier Proteins ; Antibodies, Monoclonal ; Ubiquitin
    Language English
    Publishing date 2022-12-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-022-25665-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Book: Abortion law in transnational perspective

    Cook, Rebecca J. / Erdman, Joanna N. / Dickens, Bernard Morris

    cases and controversies

    (Pennsylvania studies in human rights)

    2014  

    Author's details edited by Rebecca J. Cook, Joanna N. Erdman, and Bernard M. Dickens
    Series title Pennsylvania studies in human rights
    Keywords Abortion, Induced / legislation & jurisprudence ; Abortion/Law and legislation
    Subject code 342.08/4
    Language English
    Size vii, 472 Seiten, 24 cm
    Edition 1st ed.
    Publisher University of Pennsylvania Press
    Publishing place Philadelphia
    Publishing country United States
    Document type Book
    HBZ-ID HT018982758
    ISBN 978-0-8122-4627-8 ; 0-8122-4627-6
    Database Catalogue ZB MED Medicine, Health

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  4. Article: Moving Mountains-The BRCA1 Promotion of DNA Resection.

    Densham, Ruth M / Morris, Joanna R

    Frontiers in molecular biosciences

    2019  Volume 6, Page(s) 79

    Abstract: DNA double-strand breaks (DSBs) occur in our cells in the context of chromatin. This type of lesion is toxic, entirely preventing genome continuity and causing cell death or terminal arrest. Several repair mechanisms can act on DNA surrounding a DSB, ... ...

    Abstract DNA double-strand breaks (DSBs) occur in our cells in the context of chromatin. This type of lesion is toxic, entirely preventing genome continuity and causing cell death or terminal arrest. Several repair mechanisms can act on DNA surrounding a DSB, only some of which carry a low risk of mutation, so that which repair process is utilized is critical to the stability of genetic material of cells. A key component of repair outcome is the degree of DNA resection directed to either side of the break site. This in turn determines the subsequent forms of repair in which DNA homology plays a part. Here we will focus on chromatin and chromatin-bound complexes which constitute the "mountains" that block resection, with a particular focus on how the breast and ovarian cancer predisposition protein-1 (BRCA1) contributes to repair outcomes through overcoming these blocks.
    Language English
    Publishing date 2019-09-03
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2814330-9
    ISSN 2296-889X
    ISSN 2296-889X
    DOI 10.3389/fmolb.2019.00079
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: SUMO monoclonal antibodies vary in sensitivity, specificity, and ability to detect types of SUMO conjugate

    Alexander J. Garvin / Alexander J. Lanz / Joanna R. Morris

    Scientific Reports, Vol 12, Iss 1, Pp 1-

    2022  Volume 16

    Abstract: Abstract Monoclonal antibodies (MAb) to members of the Small Ubiquitin-like modifier (SUMO) family are essential tools in the study of cellular SUMOylation. However, many anti-SUMO MAbs are poorly validated, and antibody matching to detection format is ... ...

    Abstract Abstract Monoclonal antibodies (MAb) to members of the Small Ubiquitin-like modifier (SUMO) family are essential tools in the study of cellular SUMOylation. However, many anti-SUMO MAbs are poorly validated, and antibody matching to detection format is without an evidence base. Here we test the specificity and sensitivity of twenty-four anti-SUMO MAbs towards monomeric and polymeric SUMO1-4 in dot-blots, immunoblots, immunofluorescence and immunoprecipitation. We find substantial variability between SUMO MAbs for different conjugation states, for detecting increased SUMOylation in response to thirteen different stress agents, and as enrichment reagents for SUMOylated RanGAP1 or KAP1. All four anti-SUMO4 monoclonal antibodies tested cross-reacted wit SUMO2/3, and several SUMO2/3 monoclonal antibodies cross-reacted with SUMO4. These data characterize the specificity of twenty-four anti-SUMO antibodies across commonly used assays, creating an enabling resource for the SUMO research community.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2022-12-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Exercise-based rehabilitation programmes for pulmonary hypertension.

    Morris, Norman R / Kermeen, Fiona D / Jones, Arwel W / Lee, Joanna Yt / Holland, Anne E

    The Cochrane database of systematic reviews

    2023  Volume 3, Page(s) CD011285

    Abstract: Background: Individuals with pulmonary hypertension (PH) have reduced exercise capacity and quality of life. Despite initial concerns that exercise training may worsen symptoms in this group, several studies have reported improvements in functional ... ...

    Abstract Background: Individuals with pulmonary hypertension (PH) have reduced exercise capacity and quality of life. Despite initial concerns that exercise training may worsen symptoms in this group, several studies have reported improvements in functional capacity and well-being following exercise-based rehabilitation.
    Objectives: To evaluate the benefits and harms of exercise-based rehabilitation for people with PH compared with usual care or no exercise-based rehabilitation.
    Search methods: We used standard, extensive Cochrane search methods. The latest search date was 28 June 2022.
    Selection criteria: We included randomised controlled trials (RCTs) in people with PH comparing supervised exercise-based rehabilitation programmes with usual care or no exercise-based rehabilitation.
    Data collection and analysis: We used standard Cochrane methods. Our primary outcomes were 1. exercise capacity, 2. serious adverse events during the intervention period and 3. health-related quality of life (HRQoL). Our secondary outcomes were 4. cardiopulmonary haemodynamics, 5. Functional Class, 6. clinical worsening during follow-up, 7. mortality and 8. changes in B-type natriuretic peptide. We used GRADE to assess certainty of evidence.
    Main results: We included eight new studies in the current review, which now includes 14 RCTs. We extracted data from 11 studies. The studies had low- to moderate-certainty evidence with evidence downgraded due to inconsistencies in the data and performance bias. The total number of participants in meta-analyses comparing exercise-based rehabilitation to control groups was 462. The mean age of the participants in the 14 RCTs ranged from 35 to 68 years. Most participants were women and classified as Group I pulmonary arterial hypertension (PAH). Study durations ranged from 3 to 25 weeks. Exercise-based programmes included both inpatient- and outpatient-based rehabilitation that incorporated both upper and lower limb exercise. The mean six-minute walk distance following exercise-based rehabilitation was 48.52 metres higher than control (95% confidence interval (CI) 33.42 to 63.62; I² = 72%; 11 studies, 418 participants; low-certainty evidence), the mean peak oxygen uptake was 2.07 mL/kg/min higher than control (95% CI 1.57 to 2.57; I² = 67%; 7 studies, 314 participants; low-certainty evidence) and the mean peak power was 9.69 W higher than control (95% CI 5.52 to 13.85; I² = 71%; 5 studies, 226 participants; low-certainty evidence). Three studies reported five serious adverse events; however, exercise-based rehabilitation was not associated with an increased risk of serious adverse event (risk difference 0, 95% CI -0.03 to 0.03; I² = 0%; 11 studies, 439 participants; moderate-certainty evidence). The mean change in HRQoL for the 36-item Short Form (SF-36) Physical Component Score was 3.98 points higher (95% CI 1.89 to 6.07; I² = 38%; 5 studies, 187 participants; moderate-certainty evidence) and for the SF-36 Mental Component Score was 3.60 points higher (95% CI 1.21 to 5.98 points; I² = 0%; 5 RCTs, 186 participants; moderate-certainty evidence). There were similar effects in the subgroup analyses for participants with Group 1 PH versus studies of groups with mixed PH. Two studies reported mean reduction in mean pulmonary arterial pressure following exercise-based rehabilitation (mean reduction: 9.29 mmHg, 95% CI -12.96 to -5.61; I² = 0%; 2 studies, 133 participants; low-certainty evidence).
    Authors' conclusions: In people with PH, supervised exercise-based rehabilitation may result in a large increase in exercise capacity. Changes in exercise capacity remain heterogeneous and cannot be explained by subgroup analysis. It is likely that exercise-based rehabilitation increases HRQoL and is probably not associated with an increased risk of a serious adverse events. Exercise training may result in a large reduction in mean pulmonary arterial pressure. Overall, we assessed the certainty of the evidence to be low for exercise capacity and mean pulmonary arterial pressure, and moderate for HRQoL and adverse events. Future RCTs are needed to inform the application of exercise-based rehabilitation across the spectrum of people with PH, including those with chronic thromboembolic PH, PH with left-sided heart disease and those with more severe disease.
    MeSH term(s) Female ; Humans ; Adult ; Middle Aged ; Aged ; Male ; Hypertension, Pulmonary ; Exercise Therapy/adverse effects ; Quality of Life ; Exercise ; Bias
    Language English
    Publishing date 2023-03-22
    Publishing country England
    Document type Systematic Review ; Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ISSN 1469-493X
    ISSN (online) 1469-493X
    DOI 10.1002/14651858.CD011285.pub3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: A fork in the road: Where homologous recombination and stalled replication fork protection part ways.

    Tye, Stephanie / Ronson, George E / Morris, Joanna R

    Seminars in cell & developmental biology

    2020  Volume 113, Page(s) 14–26

    Abstract: In response to replication hindrances, DNA replication forks frequently stall and are remodelled into a four-way junction. In such a structure the annealed nascent strand is thought to resemble a DNA double-strand break and remodelled forks are ... ...

    Abstract In response to replication hindrances, DNA replication forks frequently stall and are remodelled into a four-way junction. In such a structure the annealed nascent strand is thought to resemble a DNA double-strand break and remodelled forks are vulnerable to nuclease attack by MRE11 and DNA2. Proteins that promote the recruitment, loading and stabilisation of RAD51 onto single-stranded DNA for homology search and strand exchange in homologous recombination (HR) repair and inter-strand cross-link repair also act to set up RAD51-mediated protection of nascent DNA at stalled replication forks. However, despite the similarities of these pathways, several lines of evidence indicate that fork protection is not simply analogous to the RAD51 loading step of HR. Protection of stalled forks not only requires separate functions of a number of recombination proteins, but also utilises nucleases important for the resection steps of HR in alternative ways. Here we discuss how fork protection arises and how its differences with HR give insights into the differing contexts of these two pathways.
    MeSH term(s) DNA Damage/genetics ; DNA Replication/genetics ; Genomic Instability/genetics ; Homologous Recombination/genetics ; Humans
    Language English
    Publishing date 2020-07-09
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1312473-0
    ISSN 1096-3634 ; 1084-9521
    ISSN (online) 1096-3634
    ISSN 1084-9521
    DOI 10.1016/j.semcdb.2020.07.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: BRCA1-BARD1: the importance of being in shape.

    Daza-Martin, Manuel / Densham, Ruth M / Morris, Joanna R

    Molecular & cellular oncology

    2019  Volume 6, Issue 6, Page(s) e1656500

    Abstract: The breast cancer type-1 susceptibility protein (BRCA1) contributes to genome integrity through homologous recombinational DNA repair and by protecting stalled replication forks from nucleolytic degradation. We recently discovered that fork protection ... ...

    Abstract The breast cancer type-1 susceptibility protein (BRCA1) contributes to genome integrity through homologous recombinational DNA repair and by protecting stalled replication forks from nucleolytic degradation. We recently discovered that fork protection requires a conformational change of BRCA1 unimportant to homologous recombination repair, indicating separate roles for BRCA1 in these pathways.
    Language English
    Publishing date 2019-09-11
    Publishing country United States
    Document type Journal Article
    ISSN 2372-3556
    ISSN 2372-3556
    DOI 10.1080/23723556.2019.1656500
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: SUMO, a small, but powerful, regulator of double-strand break repair.

    Garvin, Alexander J / Morris, Joanna R

    Philosophical transactions of the Royal Society of London. Series B, Biological sciences

    2017  Volume 372, Issue 1731

    Abstract: The response to a DNA double-stranded break in mammalian cells is a process of sensing and signalling the lesion. It results in halting the cell cycle and local transcription and in the mediation of the DNA repair process itself. The response is launched ...

    Abstract The response to a DNA double-stranded break in mammalian cells is a process of sensing and signalling the lesion. It results in halting the cell cycle and local transcription and in the mediation of the DNA repair process itself. The response is launched through a series of post-translational modification signalling events coordinated by phosphorylation and ubiquitination. More recently modifications of proteins by
    MeSH term(s) Animals ; DNA Breaks, Double-Stranded ; DNA Repair ; Humans ; Mammals/genetics ; Small Ubiquitin-Related Modifier Proteins/metabolism ; Sumoylation
    Chemical Substances Small Ubiquitin-Related Modifier Proteins
    Language English
    Publishing date 2017-08-28
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 208382-6
    ISSN 1471-2970 ; 0080-4622 ; 0264-3839 ; 0962-8436
    ISSN (online) 1471-2970
    ISSN 0080-4622 ; 0264-3839 ; 0962-8436
    DOI 10.1098/rstb.2016.0281
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: SUMO in the DNA Double-Stranded Break Response: Similarities, Differences, and Cooperation with Ubiquitin.

    Morris, Joanna R / Garvin, Alexander J

    Journal of molecular biology

    2017  Volume 429, Issue 22, Page(s) 3376–3387

    Abstract: In recent years, our knowledge of the varied role that ubiquitination plays in promoting signal amplification, novel protein interactions, and protein turnover has progressed rapidly. This is particularly remarkable in the examination of how DNA double- ... ...

    Abstract In recent years, our knowledge of the varied role that ubiquitination plays in promoting signal amplification, novel protein interactions, and protein turnover has progressed rapidly. This is particularly remarkable in the examination of how DNA double-stranded breaks (DSBs) are repaired, with many components of the ubiquitin (Ub) conjugation, de-conjugation, and recognition machinery now identified as key factors in DSB repair. In addition, a member of the Ub-like family, small Ub-like modifier (SUMO), has also been recognised as integral for efficient repair. Here, we summarise our emerging understanding of SUMOylation both as a distinct modification and as a cooperative modification with Ub, using the cellular response to DNA DSBs as the primary setting to compare these modifications.
    MeSH term(s) DNA Breaks, Double-Stranded ; DNA Repair ; Eukaryotic Cells/enzymology ; Eukaryotic Cells/physiology ; Small Ubiquitin-Related Modifier Proteins/metabolism ; Sumoylation ; Ubiquitin/metabolism
    Chemical Substances Small Ubiquitin-Related Modifier Proteins ; Ubiquitin
    Language English
    Publishing date 2017-05-17
    Publishing country Netherlands
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 80229-3
    ISSN 1089-8638 ; 0022-2836
    ISSN (online) 1089-8638
    ISSN 0022-2836
    DOI 10.1016/j.jmb.2017.05.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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