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Expression levels of the human DNA repair protein metnase influence lentiviral genomic integration.

ABSTRACT: We recently identified a Transposase domain protein called Metnase, which assists in repairing DNA double-strand breaks (DSB) via non-homologous end-joining (NHEJ), and is important for foreign DNA integration into a host cell genome. Since integration is essential for productive lentiviral infection we examined whether Metnase expression levels could have an influence on lentiviral genomic integration. Using cells stably transduced to either over- or under-express Metnase we determined that the expression level of Metnase did indeed correlate with live lentiviral integration. Changes in Metnase levels were accompanied by changes in the number of copies of integrated lentiviral cDNA. While Metnase levels affected lentiviral integration, it had no effect on the amount of either total cellular viral RNA, cDNA or 2-LTR circles. Therefore, Metnase enhances the integration of lentivirus DNA into the host cell genome.

SUBMITTER: Williamson EA

PROVIDER: S-EPMC2556226 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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Expression levels of the human DNA repair protein metnase influence lentiviral genomic integration.

Williamson Elizabeth A EA Farrington Jacqueline J Martinez Leah L Ness Scott S O'Rourke John J Lee Suk-Hee SH Nickoloff Jac J Hromas Robert R

Biochimie 20080523 9

We recently identified a Transposase domain protein called Metnase, which assists in repairing DNA double-strand breaks (DSB) via non-homologous end-joining (NHEJ), and is important for foreign DNA integration into a host cell genome. Since integration is essential for productive lentiviral infection we examined whether Metnase expression levels could have an influence on lentiviral genomic integration. Using cells stably transduced to either over- or under-express Metnase we determined that the ...[more]

PMID: 18549821

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Project description:Breast cancer (BC) is the most commonly diagnosed cancer in women worldwide and is the leading cause of death among Hispanic women. Previous studies have shown that women with a low DNA repair capacity (DRC), measured through the nucleotide excision repair (NER) pathway, have an increased BC risk. Moreover, we previously reported an association between DRC levels and the expression of the microRNA (miRNA) let-7b in BC patients. MiRNAs can induce genomic instability by affecting the cell's DNA damage response while influencing the cancer pathobiology. The aim of this pilot study is to identify plasma miRNAs related to variations in DRC levels in BC cases. Hypothesis. Our hypothesis consists in testing whether DRC levels can be correlated with miRNA expression levels. Methods. Plasma samples were selected from 56 (27 cases and 29 controls) women recruited as part of our BC cohort. DRC values were measured in lymphocytes using the host-cell reactivation assay. The samples were divided into two categories: low (≤3.8%) and high (>3.8%) DRC levels. MiRNAs were extracted to perform an expression profile analysis. Results. Forty miRNAs were identified to be BC-related (p<0.05, MW), while 18 miRNAs were found to be differentially expressed among BC cases and controls with high and low DRC levels (p<0.05, KW). Among these candidates are miR-299-5p, miR-29b-3p, miR-302c-3p, miR-373-3p, miR-636, miR-331-5p, and miR-597-5p. Correlation analyses revealed that 4 miRNAs were negatively correlated within BC cases with low DRC (p<0.05, Spearman's correlation). Results from multivariate analyses revealed that the clinicopathological characteristics may not have a direct effect on specific miRNA expression. Conclusion. This pilot study provides evidence of four miRNAs that are negatively regulated in BC cases with low DRC levels. Additional studies are needed in order to have a complete framework regarding the overall DRC levels, miRNA expression profiles, and tumor characteristics.

Dataset Information

Expression levels of the human DNA repair protein metnase influence lentiviral genomic integration.

Publications

Expression levels of the human DNA repair protein metnase influence lentiviral genomic integration.

Similar Datasets

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