RESUMEN
XR-1 is a Chinese hamster ovary (CHO) cell mutant which is unusually sensitive to killing by gamma rays in the G1 portion of the cell cycle but has nearly normal resistance to gamma-ray damage in late S phase. The cell-cycle sensitivity correlates with the mutant's inability to repair DNA double-strand breaks (DSBs) produced by ionizing radiation and restriction enzymes. We have previously shown in somatic cell hybrids of XR-1 cells and human fibroblasts that the XR-1 mutation is a recessive mutation. In this study, using somatic cell hybrids formed between XR-1 and human fibroblasts, we map the human complementing gene to chromosome 5 by chromosome-segregation analysis. This gene biochemically restores the hamster defect to wild-type levels of gamma-ray and bleomycin resistance as well as restoring its proficiency to repair DNA DSBs, suggesting that a single gene is responsible for the XR-1 phenotype. We have tentatively assigned the name XRCC4 (X-ray-complementing Chinese hamster gene 4) to this human gene until its biochemical function in repair is discovered.
Asunto(s)
Cromosomas Humanos Par 5 , Daño del ADN , Reparación del ADN , Animales , Bleomicina/farmacología , Ciclo Celular , Línea Celular , Mapeo Cromosómico , Cricetinae , ADN/efectos de la radiación , Resistencia a Medicamentos , Fibroblastos , Rayos gamma , Prueba de Complementación Genética , Humanos , Células Híbridas , Cariotipificación , Mutación , FenotipoRESUMEN
A female infant born to a mother with active Graves disease and a strongly positive LATS developed neonatal thyrotoxicosis. The diagnosis was confirmed rapidly by the markedly elevated filter paper spot T4 (5.45 ng/40 microliter) taken on the fifth day of life as part of the Quebec Screening Program for Neonatal Hypothyroidism. Although the infant's serum was negative for LATS, it reacted strongly (as did the maternal serum) in the lipolytic assay for LATS. This case illustrates the ability of screening programs for neonatal hypothyroidism to detect cases of neonatal thyrotoxicosis and supports the hypothesis that this condition is secondary to the placental transfer of a thyroid-stimulating immunoglobulin.