R A Katz

..Lastly, we observed that ASV can transduce postmitotic mouse neurons. These results support an active nuclear import mechanism for the oncoretrovirus ASV and suggest that this mechanism can operate in both nondividing and dividing cells...

..We conclude that efficient nuclear entry can occur independently of mitotic nuclear disassembly in cycling cells...

..However, all retroviruses are subject to a variety of cell cycle restrictions. Here, we discuss such restrictions, and how they may block retroviral replication, be tolerated, or overcome...

..We conclude that HDACs can act rapidly to initiate and maintain promoter-independent retroviral epigenetic repression and silencing but that reactivation can be restricted by additional mechanisms...

..From these results we propose that such unpairing may enhance both the processing and the joining steps in the integration reaction, and perhaps other cellular recombination reactions as well...

..Furthermore, these results are consistent with our previous observations indicating that unpairing of target DNA promotes the joining reaction...

..The studies also suggest that cells can be sensitized to such killing and stable retroviral DNA integration blocked by drugs that inhibit cellular DNA repair pathways...

..Here, we review these findings and discuss other ways that retroviral DNA intermediates may interact with the host DNA damage signaling and repair pathways...

..In this paper, using two independent assays, we demonstrate that IN, alone, is sufficient to carry out the second step: cleavage and joining to the target DNA. These results demonstrate that the retroviral IN protein is an integrase...

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..These results indicate that the DNA repair pathway which compensates for loss of NHEJ in these transductants does not introduce any gross abnormalities at the provirus-host DNA junctions...

..These results suggest that the initial events in retroviral integration are detected as DNA damage by the host cell and that completion of the integration process requires the DNA-PK-mediated repair pathway...

..Furthermore, this retroviral system provides a powerful genetic method for selection and analysis of mutations that affect splicing control...

..Furthermore pepstatin, a strong inhibitor of pepsin, renin, and cathepsin-D has little effect on PR...

..Our findings provide a novel example of cellular immunity against viral replication in which viral transcription is repressed via the recruitment of antiviral proteins to the viral DNA...

..Such differences may be relevant to viral pathogenesis and provide utility in retroviral vector design...

..These observations provide independent support for an anchoring model for the function of gammaH2AX in chromatin repair...

..Results presented in this study lend further support to a general role for the NHEJ DNA repair pathway in completion of the retroviral DNA integration process...

..These distinct properties of integrases may also affect target site selection in vivo, resulting in an important bias against or in favor of integration into actively transcribed host DNA...

..The transduction efficiency of the ASV vector was found to be intermediate between the relatively high and low efficiencies obtained with human immunodeficiency virus type 1 and murine leukemia virus vectors, respectively...

..Components of the cellular DNA damage repair response may represent potential targets for antiretroviral drug development...

..Furthermore, our results indicate that siRNAs can be used as specific reagents to interrupt the maintenance of epigenetic silencing...