Human DNA repair gene XRCC1 complements the strand-break rejoining defect in Chinese hamster mutant EM9 and encodes a protein that is apparently required for optimal activity of DNA ligase III. Toward the goal of producing transgenic mice that carry a mutation in the Xrcc-1 locus, the murine homolog of XRCC1 was cloned from both cosmid genomic and cDNA libraries. Upon transfection into EM9 cells, cosmids containing the functional mouse gene efficiently corrected (94-100%) the high sister-chromatid-exchange defect. Mouse Xrcc-1 is 26 kb in length, contains 17 exons, and maps by metaphase in situ hybridization to the 7A3-7B2 region of mouse chromosome 7. Isolated cDNA clones were highly truncated and were extended by anchored polymerase chain reactions. The 1893-bp open reading frame of mouse Xrcc-1 encodes 631 amino acids, compared with 633 for the human homolog. The predicted mouse Xrcc-1 protein of 69.1 kDa and pI of 5.95 is 86% identical and 93% similar to human XRCC1.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1006/geno.1994.1359 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Recent studies have shown that IL-6 signaling plays an important role in the aggressive and metastatic phenotype of head and neck squamous cell carcinoma (HNSCC). Therefore, we hypothesized that targeting of IL-6 signaling in HNSCC could enhance the therapeutic efficacy of standard chemoradiation treatment. We used both and models to test the efficacy of Bazedoxifene (BZA), a drug that was originally developed as a newer-generation selective estrogen receptor modulator (SERM) for the treatment of postmenopausal osteoporosis.
View Article and Find Full Text PDFSorafenib enhances the antitumor effects of chemoradiation treatment by downregulating ERCC-1 and XRCC-1 DNA repair proteins.
Mol Cancer Ther
July 2011
The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
Head and neck squamous cell carcinoma remains a challenging clinical problem because of the persisting high rate of local and distant failure due to the acquisition of chemo- and radioresistance. In this study, we examined if treatment with sorafenib, a potent inhibitor of Raf kinase and VEGF receptor, could reverse the resistant phenotype in tumor and tumor-associated endothelial cells, thereby enhancing the therapeutic efficacy of currently used chemoradiation treatment. We used both in vitro and in vivo models to test the efficacy of sorafenib either as a single agent or in combination with chemoradiation.
View Article and Find Full Text PDFRequirement for the Xrcc1 DNA base excision repair gene during early mouse development.
Dev Biol
April 1999
Department of Dermatology, University of California at San Francisco, San Francisco, California, 94143, USA.
Surveillance and repair of DNA damage are essential for maintaining the integrity of the genetic information that is needed for normal development. Several multienzyme pathways, including the excision repair of damaged or missing bases, carry out DNA repair in mammals. We determined the developmental role of the X-ray cross-complementing (Xrcc)-1 gene, which is central to base excision repair, by generating a targeted mutation in mice.
View Article and Find Full Text PDFXrcc-1 expression during male meiosis in the mouse.
Biol Reprod
September 1996
Department of Cellular and Structural Biology, University of Texas Health Science, Center at San Antonio 78284-7762, USA.
XRCC1 is involved in DNA strand-break repair, homologous recombination, and sister chromatid exchange and is expressed as a low-abundance mRNA with elevated expression in testis. The purpose of this study was to determine whether specific spermatogenic cell types have elevated Xrcc-1 expression and whether expression levels change in the testis with increased age. Northern blot analysis of mRNA prepared from testes of 15-, 25-, and 60-day-old mice revealed a single hybridizing band of 2.
View Article and Find Full Text PDFTestis and somatic Xrcc-1 DNA repair gene expression.
Somat Cell Mol Genet
November 1994
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio 78284-7762.
The human XRCC1 gene has been shown to be involved in DNA strand-break repair using the Chinese hamster ovary cell mutant EM9. The purpose of this study was to characterize the expression of Xrcc-1 to determine if there is tissue-specific expression and to provide a baseline of information for future studies that may involve altering Xrcc-1 expression in mice. Normal young adult male testis and enriched populations of pachytene spermatocytes and round spermatids displayed significantly higher levels of Xrcc-1 expression than other mouse tissues, although Xrcc-1 transcripts were found in low abundance in all tested tissues.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!