Genetics. Published Articles Ahead of Print: April 30, 2006, Copyright © 2006
doi:10.1534/genetics.106.058081


A more recent version of this article appeared on July 1, 2006.

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The Drosophila Nbs protein functions in multiple pathways for the maintenance of genome stability

Laura Ciapponi 1, Giovanni Cenci 2 and Maurizio Gatti 1*

1 University of Rome
2 University of Lecce

* To whom correspondence should be addressed. E-mail: maurizio.gatti{at}uniroma1.it.

Submitted on March 10, 2006
Revised on April 14, 2006
Accepted on 29 April 2006


Abstract

The Mre11/Rad50/Nbs (MRN) complex and the two protein kinases ATM and ATR play critical roles in the response to DNA damage and telomere maintenance in mammalian systems. It has been previously shown that mutations in the Drosophila mre11 and rad50 genes cause both telomere fusion and chromosome breakage. Here, we have analyzed the role of the Drosophila nbs gene in telomere protection and the maintenance of chromosome integrity. Larval brain cells of nbs mutants display telomeric associations (TAs) but the frequency of these TAs is lower than in either mre11 and rad50 mutants. Consistently, Rad50 accumulates in the nuclei of wild type cells but not in those of nbs cells, indicating that Nbs mediates transport of the Mre11/Rad50 complex in the nucleus. Moreover, epistasis analysis revealed that rad50 nbs, tefu (ATM) nbs and mei-41 (ATR) nbs double mutants have significantly higher frequencies of TAs than either of the corresponding single mutants. This suggests that Nbs and the Mre11/Rad50 complex play partially independent roles in telomere protection, and that Nbs functions in both an ATR- and an ATM-controlled telomere protection pathway. In contrast, analysis of chromosome breakage indicated that the three components of the MRN complex function in a single pathway for the repair of the DNA damage leading to chromosome aberrations.

Key Words: Drosophila, Nbs, chromosome aberrations, telomere, telomeric fusion