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Alterations in expression and structure of the DNA repair gene XRCC1
1Department of Molecular Pathology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Abstract:
The repair-associated gene XRCC1 was previously cloned by complementing the hamster mutant EM9, which has a high rate of spontaneous SCE and hypersensitivity to DNA damaging agents. In analyzing XRCC1 gene expression, similar levels of steady-state mRNA were found in normal cells, Bloom's syndrome cells with altered SCE, and in squamous carcinoma cells with differential X-ray sensitivity. An EcoRI restriction fragment-length polymorphism previously identified in XRCC1 did not correlate with the repair phenotypes of these cells. The mRNA of XRCC1 decreased to 20-40% after treatment of cells with a DNA damaging agent. XRCC1 also showed tissue specific expression in rats. The mRNA levels were high in testis (7-8 fold), ovary (3-4 fold) and brain (4-5 fold), when compared with those in intestine, liver and spleen (1-2 fold). These data and the high levels of XRCC1 protein detected in testis indicate that XRCC1 may play an important role in DNA processing during meiogenesis and recombination in germ cells.