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  1. Article ; Online: Integrating Opioid Use Disorder Treatment Into Primary Care Settings.

    Austin, Elizabeth J / Chen, Jessica / Briggs, Elsa S / Ferro, Lori / Barry, Paul / Heald, Ashley / Merrill, Joseph O / Curran, Geoffrey M / Saxon, Andrew J / Fortney, John C / Ratzliff, Anna D / Williams, Emily C

    JAMA network open

    2023  Volume 6, Issue 8, Page(s) e2328627

    Abstract: Importance: Medication for opioid use disorder (MOUD) (eg, buprenorphine and naltrexone) can be offered in primary care, but barriers to implementation exist.: Objective: To evaluate an implementation intervention over 2 years to explore experiences ... ...

    Abstract Importance: Medication for opioid use disorder (MOUD) (eg, buprenorphine and naltrexone) can be offered in primary care, but barriers to implementation exist.
    Objective: To evaluate an implementation intervention over 2 years to explore experiences and perspectives of multidisciplinary primary care (PC) teams initiating or expanding MOUD.
    Design, setting, and participants: This survey-based and ethnographic qualitative study was conducted at 12 geographically and structurally diverse primary care clinics that enrolled in a hybrid effectiveness-implementation study from July 2020 to July 2022 and included PC teams (prescribing clinicians, nonprescribing behavioral health care managers, and consulting psychiatrists). Survey data analysis was conducted from February to April 2022.
    Exposure: Implementation intervention (external practice facilitation) to integrate OUD treatment alongside existing collaborative care for mental health services.
    Measures: Data included (1) quantitative surveys of primary care teams that were analyzed descriptively and triangulated with qualitative results and (2) qualitative field notes from ethnographic observation of clinic implementation meetings analyzed using rapid assessment methods.
    Results: Sixty-two primary care team members completed the survey (41 female individuals [66%]; 1 [2%] American Indian or Alaskan Native, 4 [7%] Asian, 5 [8%] Black or African American, 5 [8%] Hispanic or Latino, 1 [2%] Native Hawaiian or Other Pacific Islander, and 46 [4%] White individuals), of whom 37 (60%) were between age 25 and 44 years. An analysis of implementation meetings (n = 362) and survey data identified 4 themes describing multilevel factors associated with PC team provision of MOUD during implementation, with variation in their experience across clinics. Themes characterized challenges with clinical administrative logistics that limited the capacity to provide rapid access to care and patient engagement as well as clinician confidence to discuss aspects of MOUD care with patients. These challenges were associated with conflicting attitudes among PC teams toward expanding MOUD care.
    Conclusions and relevance: The results of this survey and qualitative study of PC team perspectives suggest that PC teams need flexibility in appointment scheduling and the capacity to effectively engage patients with OUD as well as ongoing training to maintain clinician confidence in the face of evolving opioid-related clinical issues. Future work should address structural challenges associated with workload burden and limited schedule flexibility that hinder MOUD expansion in PC settings.
    MeSH term(s) Adult ; Female ; Humans ; Ambulatory Care Facilities/organization & administration ; Ambulatory Care Facilities/statistics & numerical data ; American Indian or Alaska Native/statistics & numerical data ; Analgesics, Opioid/therapeutic use ; Opioid-Related Disorders/drug therapy ; Opioid-Related Disorders/epidemiology ; Opioid-Related Disorders/ethnology ; Primary Health Care/methods ; Primary Health Care/organization & administration ; Primary Health Care/statistics & numerical data ; Male ; Patient Care Team/statistics & numerical data ; Asian/statistics & numerical data ; Black or African American/statistics & numerical data ; Hispanic or Latino/statistics & numerical data ; Native Hawaiian or Other Pacific Islander/statistics & numerical data ; White/statistics & numerical data ; Appointments and Schedules ; Workload
    Chemical Substances Analgesics, Opioid
    Language English
    Publishing date 2023-08-01
    Publishing country United States
    Document type Journal Article ; Multicenter Study
    ISSN 2574-3805
    ISSN (online) 2574-3805
    DOI 10.1001/jamanetworkopen.2023.28627
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  2. Article ; Online: Integrating Routine Screening for Opioid Use Disorder into Primary Care Settings: Experiences from a National Cohort of Clinics.

    Austin, Elizabeth J / Briggs, Elsa S / Ferro, Lori / Barry, Paul / Heald, Ashley / Curran, Geoffrey M / Saxon, Andrew J / Fortney, John / Ratzliff, Anna D / Williams, Emily C

    Journal of general internal medicine

    2022  Volume 38, Issue 2, Page(s) 332–340

    Abstract: Background: The U.S. Preventive Services Task Force recommends routine population-based ...

    Abstract Background: The U.S. Preventive Services Task Force recommends routine population-based screening for drug use, yet screening for opioid use disorder (OUD) in primary care occurs rarely, and little is known about barriers primary care teams face.
    Objective: As part of a multisite randomized trial to provide OUD and behavioral health treatment using the Collaborative Care Model, we supported 10 primary care clinics in implementing routine OUD screening and conducted formative evaluation to characterize early implementation experiences.
    Design: Qualitative formative evaluation.
    Approach: Formative evaluation included taking detailed observation notes at implementation meetings with individual clinics and debriefings with external facilitators. Observation notes were analyzed weekly using a Rapid Assessment Process guided by the Consolidated Framework for Implementation Research, with iterative feedback from the study team. After clinics launched OUD screening, we conducted structured fidelity assessments via group interviews with each site to evaluate clinic experiences with routine OUD screening. Data from observation and structured fidelity assessments were combined into a matrix to compare across clinics and identify cross-cutting barriers and promising implementation strategies.
    Key results: While all clinics had the goal of implementing population-based OUD screening, barriers were experienced across intervention, individual, and clinic setting domains, with compounding effects for telehealth visits. Seven themes emerged characterizing barriers, including (1) challenges identifying who to screen, (2) complexity of the screening tool, (3) staff discomfort and/or hesitancies, (4) workflow barriers that decreased screening follow-up, (5) staffing shortages and turnover, (6) discouragement from low screening yield, and (7) stigma. Promising implementation strategies included utilizing a more universal screening approach, health information technology (HIT), audit and feedback, and repeated staff trainings.
    Conclusions: Integrating population-based OUD screening in primary care is challenging but may be made feasible via implementation strategies and tailored practice facilitation that standardize workflows via HIT, decrease stigma, and increase staff confidence regarding OUD.
    MeSH term(s) Humans ; Opioid-Related Disorders/drug therapy ; Ambulatory Care Facilities ; Behavior Therapy ; Telemedicine ; Primary Health Care
    Language English
    Publishing date 2022-05-25
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 639008-0
    ISSN 1525-1497 ; 0884-8734
    ISSN (online) 1525-1497
    ISSN 0884-8734
    DOI 10.1007/s11606-022-07675-2
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  3. Article ; Online: Chromosomal replication initiation machinery of low-G+C-content Firmicutes.

    Briggs, Geoffrey S / Smits, Wiep Klaas / Soultanas, Panos

    Journal of bacteriology

    2012  Volume 194, Issue 19, Page(s) 5162–5170

    Abstract: Much of our knowledge of the initiation of DNA replication comes from studies in the gram-negative model organism Escherichia coli. However, the location and structure of the origin of replication within the E. coli genome and the identification and ... ...

    Abstract Much of our knowledge of the initiation of DNA replication comes from studies in the gram-negative model organism Escherichia coli. However, the location and structure of the origin of replication within the E. coli genome and the identification and study of the proteins which constitute the E. coli initiation complex suggest that it might not be as universal as once thought. The archetypal low-G+C-content gram-positive Firmicutes initiate DNA replication via a unique primosomal machinery, quite distinct from that seen in E. coli, and an examination of oriC in the Firmicutes species Bacillus subtilis indicates that it might provide a better model for the ancestral bacterial origin of replication. Therefore, the study of replication initiation in organisms other than E. coli, such as B. subtilis, will greatly advance our knowledge and understanding of these processes as a whole. In this minireview, we highlight the structure-function relationships of the Firmicutes primosomal proteins, discuss the significance of their oriC architecture, and present a model for replication initiation at oriC.
    MeSH term(s) Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Chromosomes, Bacterial/genetics ; Chromosomes, Bacterial/physiology ; Computational Biology ; DNA Replication/physiology ; DNA, Bacterial/genetics ; Gene Expression Regulation, Bacterial/physiology
    Chemical Substances Bacterial Proteins ; DNA, Bacterial
    Language English
    Publishing date 2012-07-13
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2968-3
    ISSN 1098-5530 ; 0021-9193
    ISSN (online) 1098-5530
    ISSN 0021-9193
    DOI 10.1128/JB.00865-12
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Modulation of DNA damage tolerance in Escherichia coli recG and ruv strains by mutations affecting PriB, the ribosome and RNA polymerase.

    Mahdi, Akeel A / Briggs, Geoffrey S / Lloyd, Robert G

    Molecular microbiology

    2012  Volume 86, Issue 3, Page(s) 675–691

    Abstract: RecG is a DNA translocase that helps to maintain genomic integrity. Initial studies suggested a role in promoting recombination, a possibility consistent with synergism between recG and ruv null alleles and reinforced when the protein was shown to unwind ...

    Abstract RecG is a DNA translocase that helps to maintain genomic integrity. Initial studies suggested a role in promoting recombination, a possibility consistent with synergism between recG and ruv null alleles and reinforced when the protein was shown to unwind Holliday junctions. In this article we describe novel suppressors of recG and show that the pathology seen without RecG is suppressed on reducing or eliminating PriB, a component of the PriA system for replisome assembly and replication restart. Suppression is conditional, depending on additional mutations that modify ribosomal subunit S6 or one of three subunits of RNA polymerase. The latter suppress phenotypes associated with deletion of priB, enabling the deletion to suppress recG. They include alleles likely to disrupt interactions with transcription anti-terminator, NusA. Deleting priB has a different effect in ruv strains. It provokes abortive recombination and compromises DNA repair in a manner consistent with PriB being required to limit exposure of recombinogenic ssDNA. This synergism is reduced by the RNA polymerase mutations identified. Taken together, the results reveal that RecG curbs a potentially negative effect of proteins that direct replication fork assembly at sites removed from the normal origin, a facility needed to resolve conflicts between replication and transcription.
    MeSH term(s) Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; DNA Damage ; DNA Helicases/genetics ; DNA Helicases/metabolism ; DNA Repair ; DNA Replication ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; DNA-Directed RNA Polymerases/genetics ; DNA-Directed RNA Polymerases/metabolism ; Endodeoxyribonucleases/genetics ; Endodeoxyribonucleases/metabolism ; Escherichia coli/enzymology ; Escherichia coli/genetics ; Escherichia coli/metabolism ; Escherichia coli Proteins/genetics ; Escherichia coli Proteins/metabolism ; Gene Expression Regulation, Bacterial ; Mutation ; Recombination, Genetic ; Ribosomes/genetics ; Ribosomes/metabolism
    Chemical Substances Bacterial Proteins ; DNA-Binding Proteins ; Escherichia coli Proteins ; PriB protein, E coli ; RuvB protein, Bacteria ; ruvC protein, E coli ; RecG protein, E coli (145137-68-4) ; DNA-Directed RNA Polymerases (EC 2.7.7.6) ; Endodeoxyribonucleases (EC 3.1.-) ; Holliday junction DNA helicase, E coli (EC 3.6.1) ; DNA Helicases (EC 3.6.4.-)
    Language English
    Publishing date 2012-09-07
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 619315-8
    ISSN 1365-2958 ; 0950-382X
    ISSN (online) 1365-2958
    ISSN 0950-382X
    DOI 10.1111/mmi.12010
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  5. Article: Chromosomal Replication Initiation Machinery of Low-G+C-Content Firmicutes

    Briggs, Geoffrey S / Smits, Wiep Klaas / Soultanas, Panos

    Journal of bacteriology. 2012 Oct. 1, v. 194, no. 19

    2012  

    Abstract: Much of our knowledge of the initiation of DNA replication comes from studies in the Gram-negative model organism Escherichia coli. However, the location and structure of the origin of replication within the E. coli genome and the identification and ... ...

    Abstract Much of our knowledge of the initiation of DNA replication comes from studies in the Gram-negative model organism Escherichia coli. However, the location and structure of the origin of replication within the E. coli genome and the identification and study of the proteins which constitute the E. coli initiation complex suggest that it might not be as universal as once thought. The archetypal low-G+C-content Gram-positive Firmicutes initiate DNA replication via a unique primosomal machinery, quite distinct from that seen in E. coli, and an examination of oriC in the Firmicutes species Bacillus subtilis indicates that it might provide a better model for the ancestral bacterial origin of replication. Therefore, the study of replication initiation in organisms other than E. coli, such as B. subtilis, will greatly advance our knowledge and understanding of these processes as a whole. In this minireview, we highlight the structure-function relationships of the Firmicutes primosomal proteins, discuss the significance of their oriC architecture, and present a model for replication initiation at oriC.
    Keywords Bacillus subtilis ; DNA replication ; Escherichia coli ; genome ; models ; proteins ; replication origin ; structure-activity relationships
    Language English
    Dates of publication 2012-1001
    Size p. 5162-5170.
    Publishing place American Society for Microbiology
    Document type Article
    ZDB-ID 2968-3
    ISSN 1098-5530 ; 0021-9193
    ISSN (online) 1098-5530
    ISSN 0021-9193
    DOI 10.1128/JB.00865-12
    Database NAL-Catalogue (AGRICOLA)

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  6. Article ; Online: GW/SW-MST: A Groundwater/Surface-Water Method Selection Tool.

    Hammett, Steven / Day-Lewis, Frederick D / Trottier, Brett / Barlow, Paul M / Briggs, Martin A / Delin, Geoffrey / Harvey, Judson W / Johnson, Carole D / Lane, John W / Rosenberry, Donald O / Werkema, Dale D

    Ground water

    2022  Volume 60, Issue 6, Page(s) 784–791

    Abstract: Groundwater/surface-water (GW/SW) exchange and hyporheic processes are topics receiving increasing attention from the hydrologic community. Hydraulic, chemical, temperature, geophysical, and remote sensing methods are used to achieve various goals (e.g., ...

    Abstract Groundwater/surface-water (GW/SW) exchange and hyporheic processes are topics receiving increasing attention from the hydrologic community. Hydraulic, chemical, temperature, geophysical, and remote sensing methods are used to achieve various goals (e.g., inference of GW/SW exchange, mapping of bed materials, etc.), but the application of these methods is constrained by site conditions such as water depth, specific conductance, bed material, and other factors. Researchers and environmental professionals working on GW/SW problems come from diverse fields and rarely have expertise in all available field methods; hence there is a need for guidance to design field campaigns and select methods that both contribute to study goals and are likely to work under site-specific conditions. Here, we present the spreadsheet-based GW/SW-Method Selection Tool (GW/SW-MST) to help practitioners identify methods for use in GW/SW and hyporheic studies. The GW/SW-MST is a Microsoft Excel-based decision support tool in which the user selects answers to questions about GW/SW-related study goals and site parameters and characteristics. Based on user input, the tool indicates which methods from a toolbox of 32 methods could potentially contribute to achieving the specified goals at the site described.
    MeSH term(s) Groundwater ; Water ; Water Pollutants, Chemical/analysis ; Water Pollution
    Chemical Substances Water (059QF0KO0R) ; Water Pollutants, Chemical
    Language English
    Publishing date 2022-04-25
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 246212-6
    ISSN 1745-6584 ; 0017-467X
    ISSN (online) 1745-6584
    ISSN 0017-467X
    DOI 10.1111/gwat.13194
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  7. Article ; Online: Smaller total and subregional cerebellar volumes in posttraumatic stress disorder: a mega-analysis by the ENIGMA-PGC PTSD workgroup.

    Huggins, Ashley A / Baird, C Lexi / Briggs, Melvin / Laskowitz, Sarah / Hussain, Ahmed / Fouda, Samar / Haswell, Courtney / Sun, Delin / Salminen, Lauren E / Jahanshad, Neda / Thomopoulos, Sophia I / Veltman, Dick J / Frijling, Jessie L / Olff, Miranda / van Zuiden, Mirjam / Koch, Saskia B J / Nawjin, Laura / Wang, Li / Zhu, Ye /
    Li, Gen / Stein, Dan J / Ipser, Jonathan / Seedat, Soraya / du Plessis, Stefan / van den Heuvel, Leigh L / Suarez-Jimenez, Benjamin / Zhu, Xi / Kim, Yoojean / He, Xiaofu / Zilcha-Mano, Sigal / Lazarov, Amit / Neria, Yuval / Stevens, Jennifer S / Ressler, Kerry J / Jovanovic, Tanja / van Rooij, Sanne J H / Fani, Negar / Hudson, Anna R / Mueller, Sven C / Sierk, Anika / Manthey, Antje / Walter, Henrik / Daniels, Judith K / Schmahl, Christian / Herzog, Julia I / Říha, Pavel / Rektor, Ivan / Lebois, Lauren A M / Kaufman, Milissa L / Olson, Elizabeth A / Baker, Justin T / Rosso, Isabelle M / King, Anthony P / Liberzon, Isreal / Angstadt, Mike / Davenport, Nicholas D / Sponheim, Scott R / Disner, Seth G / Straube, Thomas / Hofmann, David / Qi, Rongfeng / Lu, Guang Ming / Baugh, Lee A / Forster, Gina L / Simons, Raluca M / Simons, Jeffrey S / Magnotta, Vincent A / Fercho, Kelene A / Maron-Katz, Adi / Etkin, Amit / Cotton, Andrew S / O'Leary, Erin N / Xie, Hong / Wang, Xin / Quidé, Yann / El-Hage, Wissam / Lissek, Shmuel / Berg, Hannah / Bruce, Steven / Cisler, Josh / Ross, Marisa / Herringa, Ryan J / Grupe, Daniel W / Nitschke, Jack B / Davidson, Richard J / Larson, Christine L / deRoon-Cassini, Terri A / Tomas, Carissa W / Fitzgerald, Jacklynn M / Blackford, Jennifer Urbano / Olatunji, Bunmi O / Kremen, William S / Lyons, Michael J / Franz, Carol E / Gordon, Evan M / May, Geoffrey / Nelson, Steven M / Abdallah, Chadi G / Levy, Ifat / Harpaz-Rotem, Ilan / Krystal, John H / Dennis, Emily L / Tate, David F / Cifu, David X / Walker, William C / Wilde, Elizabeth A / Harding, Ian H / Kerestes, Rebecca / Thompson, Paul M / Morey, Rajendra

    Molecular psychiatry

    2024  

    Abstract: Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map ...

    Abstract Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map on to motor, cognitive, and affective functions. In a sample of 4215 adults (PTSD n = 1642; Control n = 2573) across 40 sites from the ENIGMA-PGC PTSD working group, we employed a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation to obtain volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum volumes in PTSD compared to healthy controls (88% trauma-exposed). PTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume, as well as reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), vermis (VI, VIII), flocculonodular lobe (lobule X), and corpus medullare (all p
    Language English
    Publishing date 2024-01-10
    Publishing country England
    Document type Journal Article
    ZDB-ID 1330655-8
    ISSN 1476-5578 ; 1359-4184
    ISSN (online) 1476-5578
    ISSN 1359-4184
    DOI 10.1038/s41380-023-02352-0
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  8. Article ; Online: The RdgC protein employs a novel mechanism involving a finger domain to bind to circular DNA.

    Briggs, Geoffrey S / Yu, Jing / Mahdi, Akeel A / Lloyd, Robert G

    Nucleic acids research

    2010  Volume 38, Issue 19, Page(s) 6433–6446

    Abstract: The DNA-binding protein RdgC has been identified as an inhibitor of RecA-mediated homologous recombination in Escherichia coli. In Neisseria species, RdgC also has a role in virulence-associated antigenic variation. We have previously solved the crystal ... ...

    Abstract The DNA-binding protein RdgC has been identified as an inhibitor of RecA-mediated homologous recombination in Escherichia coli. In Neisseria species, RdgC also has a role in virulence-associated antigenic variation. We have previously solved the crystal structure of the E. coli RdgC protein and shown it to form a toroidal dimer. In this study, we have conducted a mutational analysis of residues proposed to mediate interactions at the dimer interfaces. We demonstrate that destabilizing either interface has a serious effect on in vivo function, even though a stable complex with circular DNA was still observed. We conclude that tight binding is required for inhibition of RecA activity. We also investigated the role of the RdgC finger domain, and demonstrate that it plays a crucial role in the binding of circular DNA. Together, these data allow us to propose a model for how RdgC loads onto DNA. We discuss how RdgC might inhibit RecA-mediated strand exchange, and how RdgC might be displaced by other DNA metabolism enzymes such as polymerases and helicases.
    MeSH term(s) Binding Sites ; DNA Helicases/genetics ; DNA, Circular/metabolism ; Dimerization ; Escherichia coli/genetics ; Escherichia coli Proteins/chemistry ; Escherichia coli Proteins/genetics ; Escherichia coli Proteins/metabolism ; Gene Deletion ; Models, Molecular ; Mutation ; Plasmids/metabolism ; Protein Structure, Tertiary
    Chemical Substances DNA, Circular ; Escherichia coli Proteins ; RdgC protein, E coli ; priA protein, E coli (EC 3.6.1.-) ; DNA Helicases (EC 3.6.4.-)
    Language English
    Publishing date 2010-06-04
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 186809-3
    ISSN 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
    ISSN (online) 1362-4962 ; 1362-4954
    ISSN 0301-5610 ; 0305-1048
    DOI 10.1093/nar/gkq509
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  9. Article ; Online: Is RecG a general guardian of the bacterial genome?

    Rudolph, Christian J / Upton, Amy L / Briggs, Geoffrey S / Lloyd, Robert G

    DNA repair

    2010  Volume 9, Issue 3, Page(s) 210–223

    Abstract: The RecG protein of Escherichia coli is a double-stranded DNA translocase that unwinds a variety of branched DNAs in vitro, including Holliday junctions, replication forks, D-loops and R-loops. Coupled with the reported pleiotropy of recG mutations, this ...

    Abstract The RecG protein of Escherichia coli is a double-stranded DNA translocase that unwinds a variety of branched DNAs in vitro, including Holliday junctions, replication forks, D-loops and R-loops. Coupled with the reported pleiotropy of recG mutations, this broad range of potential targets has made it hard to pin down what the protein does in vivo, though roles in recombination and replication fork repair have been suggested. However, recent studies suggest that RecG provides a more general defence against pathological DNA replication. We have postulated that this is achieved through the ability of RecG to eliminate substrates that the replication restart protein, PriA, could otherwise exploit to re-replicate the chromosome. Without RecG, PriA triggers a cascade of events that interfere with the duplication and segregation of chromosomes. Here we review the studies that led us to this idea and to conclude that RecG may be both a specialist activity and a general guardian of the genome.
    MeSH term(s) Animals ; Bacterial Proteins/chemistry ; Bacterial Proteins/metabolism ; DNA Helicases/chemistry ; DNA Helicases/metabolism ; DNA Replication ; DNA, Bacterial/chemistry ; DNA, Bacterial/genetics ; DNA, Bacterial/metabolism ; Genome, Bacterial ; Humans ; Recombination, Genetic
    Chemical Substances Bacterial Proteins ; DNA, Bacterial ; DNA Helicases (EC 3.6.4.-)
    Language English
    Publishing date 2010-01-25
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2071608-4
    ISSN 1568-7856 ; 1568-7864
    ISSN (online) 1568-7856
    ISSN 1568-7864
    DOI 10.1016/j.dnarep.2009.12.014
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  10. Article ; Online: Promoting and avoiding recombination: contrasting activities of the Escherichia coli RuvABC Holliday junction resolvase and RecG DNA translocase.

    Zhang, Jing / Mahdi, Akeel A / Briggs, Geoffrey S / Lloyd, Robert G

    Genetics

    2010  Volume 185, Issue 1, Page(s) 23–37

    Abstract: RuvABC and RecG are thought to provide alternative pathways for the late stages of recombination in Escherichia coli. Inactivation of both blocks the recovery of recombinants in genetic crosses. RuvABC resolves Holliday junctions, with RuvAB driving ... ...

    Abstract RuvABC and RecG are thought to provide alternative pathways for the late stages of recombination in Escherichia coli. Inactivation of both blocks the recovery of recombinants in genetic crosses. RuvABC resolves Holliday junctions, with RuvAB driving branch migration and RuvC catalyzing junction cleavage. RecG also drives branch migration, but no nuclease has been identified that might act with RecG to cleave junctions, apart from RusA, which is not normally expressed. We searched for an alternative nuclease using a synthetic lethality assay to screen for mutations causing inviability in the absence of RuvC, on the premise that a strain without any ability to cut junctions might be inviable. All the mutations identified mapped to polA, dam, or uvrD. None of these genes encodes a nuclease that cleaves Holliday junctions. Probing the reason for the inviability using the RusA Holliday junction resolvase provided strong evidence in each case that the RecG pathway is very ineffective at removing junctions and indicated that a nuclease component most probably does not exist. It also revealed new suppressors of recG, which were located to the ssb gene. Taken together with the results from the synthetic lethality assays, the properties of the mutant SSB proteins provide evidence that, rather than promoting recombination, a major function of RecG is to curb potentially pathological replication initiated via PriA protein at sites remote from oriC.
    MeSH term(s) Amino Acid Substitution/genetics ; Bacterial Proteins/metabolism ; Chromosomes, Bacterial/metabolism ; DNA Helicases/metabolism ; DNA Repair ; DNA Replication ; DNA, Bacterial/metabolism ; Endodeoxyribonucleases/metabolism ; Escherichia coli/cytology ; Escherichia coli/enzymology ; Escherichia coli Proteins/metabolism ; Holliday Junction Resolvases/metabolism ; Microbial Viability ; Models, Biological ; Recombination, Genetic/genetics ; Suppression, Genetic/genetics
    Chemical Substances Bacterial Proteins ; DNA, Bacterial ; Escherichia coli Proteins ; RuvB protein, Bacteria ; ruvC protein, E coli ; RecG protein, E coli (145137-68-4) ; Endodeoxyribonucleases (EC 3.1.-) ; Holliday Junction Resolvases (EC 3.1.21.-) ; Holliday junction DNA helicase, E coli (EC 3.6.1) ; DNA Helicases (EC 3.6.4.-)
    Language English
    Publishing date 2010-02-15
    Publishing country United States
    Document type Journal Article ; 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.110.114413
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