Maintenance of telomere structure by MRE11 associated with the Nijmegen breakage syndrome protein.

共济失调毛细血管扩张症（A-T）和奈梅亨断裂综合征（NBS）是常染色体隐性遗传病，与染色体畸变和癌症易感性相关。ATM和NBS （Nibrin）分别被鉴定为A-T和NBS缺失的基因产物。相关疾病共济失调-毛细血管扩张样疾病（ATLD）的细胞特征与A-T和NBS以及MRE11突变的结果相似。我们利用高重组鸡B细胞系DT40制备了条件MRE11缺陷细胞，并研究了MRE11的功能。脊椎动物Mre11是必不可少的。缺乏Mre11的DT40细胞在Mre11抑制下积累染色体断裂并死亡，表现出频繁的中心体扩增。Mre11缺乏还会导致放射敏感性增加和目标集成频率大幅降低。因此，Mre11对HR至关重要，并且通过重组修复在染色体维持中的作用在有丝分裂中至关重要。我们还观察到Mre11缺陷细胞中g链伸长的趋势，提示Mre11可能参与端粒结构的维持。

Ataxia telangiectasia (A-T) and Nijmegen breakage syndrome (NBS) are the autosomal reccessive disorders associated with frequent chromosomal aberration and predisposition to cancer. ATM and NBS (Nibrin) have been identified as the gene products deficient in A-T and NBS, respectively. The cellular features of the related disease, ataxia-telangiectasia-like disorder (ATLD) shows similar to those seen in A-T as well as NBS and results from MRE11 mutations. We have generated the conditional MRE11 deficient cells using a hyper-recombinogenic chicken B cell line, DT40 and investigated the function of Mre11. Vertebrate Mre11 is essential. Mre11 deficient DT40 cells accumulate chromosome breaks and die upon Mre11 repression, showing frequent centrosome amplification. Mre11 deficiency also causes increased radiosensitivity and strongly reduced targeted integration frequencies. Mre11 is, therefore, crucial for HR and essential in mitosis through its role in chromosome maintenance by recombinational repair. We also observed the tendency of elongated G-strand overhang in Mre11 deficient cells, suggesting that MRE11 might be involved in the maintenance of telomere structure.