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

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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.