Telomere protection without a telomerase; the role of ATM and Mre11 in Drosophila telomere maintenance.
The conserved ATM checkpoint kinase and the Mre11 DNA repair complex play essential and overlapping roles in maintaining genomic integrity. We conducted genetic and cytological studies on Drosophila atm and mre11 knockout mutants and discovered a telomere defect that was more severe than in any of the non-Drosophila systems studied. In mutant mitotic cells, an average of 30% of the chromosome ends engaged in telomere fusions. These fusions led to the formation and sometimes breakage of dicentric chromosomes, thus starting a devastating breakage-fusion-bridge cycle. Some of the fusions depended on DNA ligase IV, which suggested that they occurred by a nonhomologous end-joining (NHEJ) mechanism. Epistasis analyses results suggest that ATM and Mre11 might also act in the same telomere maintenance pathway in metazoans. Since Drosophila telomeres are not added by a telomerase, our findings support an additional role for both ATM and Mre11 in telomere maintenance that is independent of telomerase regulation.
Bi
Xiaolin
X
Laboratory of Molecular Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Wei
Su-Chin D
SC
Rong
Yikang S
YS
D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D015139:Blotting, Southern; D018797:Cell Cycle Proteins; D043171:Chromosomal Instability / Q000235:genetics; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000378:metabolism; D017931:DNA Primers; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins / Q000378:metabolism / Q000502:physiology*; D004706:Endodeoxyribonucleases / Q000378:metabolism / Q000502:physiology*; D004843:Epistasis, Genetic; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology*; D016615:Telomere / Q000502:physiology*; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D025521:Tumor Suppressor Proteins; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D004706:Endodeoxyribonucleases; C492904:Mre11 protein, Drosophila; D011088:DNA Ligases; D000072481:DNA Ligase ATP