Originally published as Genetics Published Articles Ahead of Print on September 9, 2008.

Genetics, Vol. 180, 741-754, October 2008, Copyright © 2008
doi:10.1534/genetics.108.089920

End Joining at Caenorhabditis elegans Telomeres

Mia Rochelle Lowden*,{dagger}, Bettina Meier*,1, Teresa Wei-sy Lee{dagger},2, Julie Hall{dagger},3 and Shawn Ahmed*,{dagger},4

* Department of Genetics and {dagger} Department of Biology, University of North Carolina, Chapel Hill, North Carolina 27599

4 Corresponding author: Department of Genetics, Coker Hall, University of North Carolina, Chapel Hill, NC 27599-3280.
E-mail: shawn{at}med.unc.edu

Critically shortened telomeres can be subjected to DNA repair events that generate end-to-end chromosome fusions. The resulting dicentric chromosomes can enter breakage–fusion–bridge cycles, thereby impeding elucidation of the structures of the initial fusion events and a mechanistic understanding of their genesis. Current models for the molecular basis of fusion of critically shortened, uncapped telomeres rely on PCR assays that typically capture fusion breakpoints created by direct ligation of chromosome ends. Here we use independent approaches that rely on distinctive features of Caenorhabditis elegans to study the frequency of direct end-to-end chromosome fusion in telomerase mutants: (1) holocentric chromosomes that allow for genetic isolation of stable end-to-end fusions and (2) unique subtelomeric sequences that allow for thorough PCR analysis of samples of genomic DNA harboring multiple end-to-end fusions. Surprisingly, only a minority of end-to-end fusion events resulted from direct end joining with no additional genome rearrangements. We also demonstrate that deficiency for the C. elegans Ku DNA repair heterodimer does not affect telomere length or cause synthetic effects in the absence of telomerase.


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Genetics 2008 180: NP. [Full Text]