Gowen L C, Avrutskaya A V, Latour A M, Koller B H, Leadon S A
Curriculum in Genetics and Molecular Biology and Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Science. 1998 Aug 14;281(5379):1009-12. doi: 10.1126/science.281.5379.1009.
The breast and ovarian cancer susceptibility gene BRCA1 encodes a zinc finger protein of unknown function. Association of the BRCA1 protein with the DNA repair protein Rad51 and changes in the phosphorylation and cellular localization of the protein after exposure to DNA-damaging agents are consistent with a role for BRCA1 in DNA repair. Here, it is shown that mouse embryonic stem cells deficient in BRCA1 are defective in the ability to carry out transcription-coupled repair of oxidative DNA damage, and are hypersensitive to ionizing radiation and hydrogen peroxide. These results suggest that BRCA1 participates, directly or indirectly, in transcription-coupled repair of oxidative DNA damage.
乳腺癌和卵巢癌易感基因BRCA1编码一种功能未知的锌指蛋白。BRCA1蛋白与DNA修复蛋白Rad51的关联，以及在暴露于DNA损伤剂后该蛋白的磷酸化和细胞定位变化，都与BRCA1在DNA修复中的作用一致。在此，研究表明，缺乏BRCA1的小鼠胚胎干细胞在进行氧化性DNA损伤的转录偶联修复能力方面存在缺陷，并且对电离辐射和过氧化氢高度敏感。这些结果表明，BRCA1直接或间接地参与氧化性DNA损伤的转录偶联修复。
