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Nucleic Acids Research Advance Access originally published online on September 25, 2007
Nucleic Acids Research 2007 35(19):6490-6500; doi:10.1093/nar/gkm472
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Nucleic Acids Research, 2007, Vol. 35, No. 19 6490-6500
© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Molecular Biology

Telomere dynamics and fusion of critically shortened telomeres in plants lacking DNA ligase IV

Michelle L. Heacock1, Rachel A. Idol1, Joanna D. Friesner2, Anne B. Britt3 and Dorothy E. Shippen1,*

1Department of Biochemistry and Biophysics, Texas A&M University 2128 TAMU, College Station, TX 77843-2128, 2Section of Molecular and Cellular Biology, UC Davis, Davis, CA, 95616 and 3Section of Plant Biology, UC Davis, Davis, CA 95616, USA

*To whom correspondence should be addressed. Tel: (979) 862 2342; Fax: (979) 845 9274; Email: dshippen{at}tamu.edu

Received April 11, 2007. Revised May 25, 2007. Accepted May 29, 2007.

In the absence of the telomerase, telomeres undergo progressive shortening and are ultimately recruited into end-to-end chromosome fusions via the non-homologous end joining (NHEJ) double-strand break repair pathway. Previously, we showed that fusion of critically shortened telomeres in Arabidopsis proceeds with approximately the same efficiency in the presence or absence of KU70, a key component of NHEJ. Here we report that DNA ligase IV (LIG4) is also not essential for telomere joining. We observed only a modest decrease (3-fold) in the frequency of chromosome fusions in triple tert ku70 lig4 mutants versus tert ku70 or tert. Sequence analysis revealed that, relative to tert ku70, chromosome fusion junctions in tert ku70 lig4 mutants contained less microhomology and less telomeric DNA. These findings argue that the KU-LIG4 independent end-joining pathway is less efficient and mechanistically distinct from KU-independent NHEJ. Strikingly, in all the genetic backgrounds we tested, chromosome fusions are initiated when the shortest telomere in the population reaches ~1 kb, implying that this size represents a critical threshold that heralds a detrimental structural transition. These data reveal the transitory nature of telomere stability, and the robust and flexible nature of DNA repair mechanisms elicited by telomere dysfunction.

Present address: Rachel A. Idol, Washington University School of Medicine, St Louis, MO 63110


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