美国研究人员日前通过动物实验发现，通过抑制53BP1基因，可降低BRCA1基因变异引发的患乳腺癌风险。这项研究报告已发表在4月1日在线刊发于美国《细胞》杂志。

        美国国家癌症研究所的研究人员报告说，此前研究显示，BRCA1基因在修复乳腺细胞DNA（脱氧核糖核酸）所受损伤方面起着重要作用，一旦这一基因发生变异，女性患乳腺癌的风险会提高85%。此次研究人员把BRCA1基因变异的实验鼠作为研究对象，对实验鼠体内名为53BP1的基因进行抑制。结果发现，这些实验鼠患癌风险大大降低。

        研究人员说，这一成果对研究通过基因抑制预防乳腺癌有重要意义。下一步，研究人员将弄清楚53BP1基因与BRCA1基因之间的相互作用。

《细胞》发表论文摘要（英文）
doi:10.1016/j.cell.2010.03.012
53BP1 Inhibits Homologous Recombination in Brca1-Deficient Cells by Blocking Resection of DNA Breaks
Samuel F. Bunting1, Elsa Callén1, 8, Nancy Wong1, 8, Hua-Tang Chen1, Federica Polato1, Amanda Gunn4, Anne Bothmer5, Niklas Feldhahn5, Oscar Fernandez-Capetillo7, Liu Cao2, Xiaoling Xu3, Chu-Xia Deng3, Toren Finkel2, Michel Nussenzweig5, 6, Jeremy M. Stark4 and André Nussenzweig1, ,
Received 21 December 2009;  revised 12 February 2010;  accepted 10 March 2010.  Published online: April 1, 2010.  Available online 1 April 2010.
Summary
Defective DNA repair by homologous recombination (HR) is thought to be a major contributor to tumorigenesis in individuals carrying Brca1 mutations. Here, we show that DNA breaks in Brca1-deficient cells are aberrantly joined into complex chromosome rearrangements by a process dependent on the nonhomologous end-joining (NHEJ) factors 53BP1 and DNA ligase 4. Loss of 53BP1 alleviates hypersensitivity of Brca1 mutant cells to PARP inhibition and restores error-free repair by HR. Mechanistically, 53BP1 deletion promotes ATM-dependent processing of broken DNA ends to produce recombinogenic single-stranded DNA competent for HR. In contrast, Lig4 deficiency does not rescue the HR defect in Brca1 mutant cells but prevents the joining of chromatid breaks into chromosome rearrangements. Our results illustrate that HR and NHEJ compete to process DNA breaks that arise during DNA replication and that shifting the balance between these pathways can be exploited to selectively protect or kill cells harboring Brca1 mutations.