• Login
    View Item 
    •   Home
    • Faculty/ Researcher Works
    • Faculty/ Researcher Works
    • View Item
    •   Home
    • Faculty/ Researcher Works
    • Faculty/ Researcher Works
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of TUScholarShareCommunitiesDateAuthorsTitlesSubjectsGenresThis CollectionDateAuthorsTitlesSubjectsGenres

    My Account

    LoginRegister

    Help

    AboutPeoplePoliciesHelp for DepositorsData DepositFAQs

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    R-Roscovitine (Seliciclib) prevents DNA damage-induced cyclin A1 upregulation and hinders non-homologous end-joining (NHEJ) DNA repair

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    R-Roscovitine (Seliciclib) ...
    Size:
    3.444Mb
    Format:
    PDF
    Download
    Genre
    Journal Article
    Date
    2010-08-04
    Author
    Federico, M
    Symonds, CE
    Bagella, L
    Rizzolio, F
    Fanale, D
    Russo, A
    Giordano, A
    Subject
    Cyclin A1
    DNA Damage
    DNA Repair
    Doxorubicin
    Hydrogen-Ion Concentration
    Protein Kinase Inhibitors
    Purines
    Roscovitine
    Up-Regulation
    Permanent link to this record
    http://hdl.handle.net/20.500.12613/5536
    
    Metadata
    Show full item record
    DOI
    10.1186/1476-4598-9-208
    Abstract
    Background: CDK-inhibitors can diminish transcriptional levels of cell cycle-related cyclins through the inhibition of E2F family members and CDK7 and 9. Cyclin A1, an E2F-independent cyclin, is strongly upregulated under genotoxic conditions and functionally was shown to increase NHEJ activity. Cyclin A1 outcompetes with cyclin A2 for CDK2 binding, possibly redirecting its activity towards DNA repair. To see if we could therapeutically block this switch, we analyzed the effects of the CDK-inhibitor R-Roscovitine on the expression levels of cyclin A1 under genotoxic stress and observed subsequent DNA damage and repair mechanisms.Results: We found that R-Roscovitine alone was unable to alter cyclin A1 transcriptional levels, however it was able to reduce protein expression through a proteosome-dependent mechanism. When combined with DNA damaging agents, R-Roscovitine was able to prevent the DNA damage-induced upregulation of cyclin A1 on a transcriptional and post-transcriptional level. This, moreover resulted in a significant decrease in non-homologous end-joining (NHEJ) paired with an increase in DNA DSBs and overall DNA damage over time. Furthermore, microarray analysis demonstrated that R-Roscovitine affected DNA repair mechanisms in a more global fashion.Conclusions: Our data reveal a new mechanism of action for R-Roscovitine on DNA repair through the inhibition of the molecular switch between cyclin A family members under genotoxic conditions resulting in reduced NHEJ capability. © 2010 Federico et al; licensee BioMed Central Ltd.
    Citation to related work
    Springer Science and Business Media LLC
    Has part
    Molecular Cancer
    ADA compliance
    For Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
    ae974a485f413a2113503eed53cd6c53
    http://dx.doi.org/10.34944/dspace/5518
    Scopus Count
    Collections
    Faculty/ Researcher Works

    entitlement

     
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Temple University Libraries | 1900 N. 13th Street | Philadelphia, PA 19122
    (215) 204-8212 | scholarshare@temple.edu
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.