Mre11-Rad50-Nbs complex is required to cap telomeres during Drosophila embryogenesis

doi:10.1073/pnas.0902707106

Mre11-Rad50-Nbs complex is required to cap telomeres during Drosophila embryogenesis

Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892

Edited by Mary-Lou Pardue, Massachusetts Institute of Technology, Cambridge, MA, and approved April 22, 2009
↵¹G.G. and X.B. contributed equally to this work. (received for review March 12, 2009)

Abstract

Using Drosophila as a model system, we identified here a stringent requirement for Mre11-Rad50-Nbs (MRN) function in telomere protection during early embryonic development. Animals homozygous for hypomorphic mutations in either mre11 or nbs develop normally with minimal telomere dysfunction. However, they produce inviable embryos that succumb to failure of mitosis caused by covalent fusion of telomeric DNA. Interestingly, the molecular defect is not the absence of MRN interaction or of Mre11 nuclease activities, but the depletion of the maternal pool of Nbs protein in these embryos. Because of Nbs depletion, Mre11 and Rad50 (MR) are excluded from chromatin. This maternal effect lethality in Drosophila is similar to that seen in mice carrying hypomorphic mrn mutations found in human patients, suggesting a common defect in telomere maintenance because of the loss of MRN integrity.

Footnotes

⁴To whom correspondence should be addressed. E-mail: rongy{at}mail.nih.gov
Author contributions: G.G., X.B., and Y.S.R. designed research; G.G., X.B., J.C., D.S., and Y.S.R. performed research; G.G., X.B., and Y.S.R. analyzed data; and G.G. and Y.S.R. wrote the paper.
↵²Present address: Laboratory for Biological Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China.
↵³Present address: Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0902707106/DCSupplemental.