Giaccia A J, Denko N, MacLaren R, Mirman D, Waldren C, Hart I, Stamato T D
Wistar Institute of Anatomy and Biology, Philadelphia, PA.
Am J Hum Genet. 1990 Sep;47(3):459-69.
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.
XR - 1是一种中国仓鼠卵巢（CHO）细胞突变体，它在细胞周期的G1期对γ射线杀伤异常敏感，但在S期后期对γ射线损伤具有近乎正常的抗性。细胞周期敏感性与该突变体无法修复由电离辐射和限制酶产生的DNA双链断裂（DSB）相关。我们之前在XR - 1细胞与人类成纤维细胞的体细胞杂种中表明，XR - 1突变是隐性突变。在本研究中，利用XR - 1与人类成纤维细胞形成的体细胞杂种，我们通过染色体分离分析将人类互补基因定位到5号染色体。该基因在生化水平上可将仓鼠的缺陷恢复到对γ射线和博来霉素抗性的野生型水平，同时恢复其修复DNA DSB的能力，这表明单个基因决定了XR - 1表型。在该人类基因在修复中的生化功能被发现之前，我们暂时将其命名为XRCC4（X射线互补中国仓鼠基因4）。
